Background: Ethiopia's sugar factories are growing by creating employment opportunities for thousands of workers with varying educational, professional, and socio-economic backgrounds. These sugar factories are a source of several physical hazards that have the potential to severely harm the workers‘ health and affect organizational productivity. In this context, comprehensive information is deficient regarding the level of physical hazard exposures, occupational health and safety practices, health outcomes, and economic costs of occupation-related injuries among sugar factory workers in Ethiopia. Objective: The study aimed to measure the level of exposure to physical hazards, occupational health and safety practices, health outcomes, and the economic costs of occupation-related injuries from the employer‘s perspective among sugar factory workers in Ethiopia. Materials and methods: A longitudinal method (objectives I and IV), a convergent parallel mixed design (objectives II), and a cross-sectional design (objectives III and V) were employed among workers in Ethiopia‘s Metehara and Wonji sugar factories. A total of 1043 eligible participants for Objectives I and IV, 1648 for Objective II, 1524 for Objective III, and 1136 for Objective V were included using the stratified random sampling technique. The homogeneous sampling method was used to carry out 20 in-depth interviews to gather qualitative data. Bagasse dust intensity was measured using a calibrated hand-held real-time dust monitor once a month for five months, totaling 50 dust samples. A generalized estimating equation model was employed, and a beta coefficient with a 95% confidence interval was used as the outcome measure (objective I). The extent of occupational health and safety practices was computed using a 21-item questionnaire. A qualitative data interpretation was created from the subject‘s perspective. The qualitative part utilized an in-depth interview guide as a tool for data collection (objective II). A Heat Stress Wet Bulb Globe Temperature meter was used to measure the amount of temperature. Heat-related symptoms were assessed through interview-administered questionnaires adapted from international health and safety guidelines (objective III). Chronic respiratory symptoms were assessed before and after the cessation of the sugarcane crushing period using the American Thoracic Society Respiratory Symptoms Questionnaire (objective IV). A top-down approach was used to compute direct costs, while the friction method was used for indirect cost estimation. A generalized linear model was used to identify the predictors of the total cost. Exponentiation coefficients with a 95% confidence interval were used to express the direction and strength of the association (objective V). Results: Time-weighted average of bagasse dust intensity in the boiler, power turbine, and evaporation plant was 8.93 mg/m3, 8.88 mg/m3, and 8.68 mg/m3, respectively. This corresponded to an exposure level to bagasse dust of 85.52% (95% CI: 83.2%–87.6%). A lack of dust control technology (β = 0.64, 95% CI: 0.53-0.75), not practicing wet spray (β = 0.27, 95% CI: 0.21- 0.41), and a lack of proper respiratory protective devices (β = 0.36, 95% CI: 0.22, 0.49) were the identified determinants of bagasse dust exposure. The overall percentage of good occupational health and safety practices was 29.6% (95% CI: 27%–32%). Associating factors of occupational health and safety practices were inappropriate provision of personal protective equipment (AOR =1.42, 95% CI=1.10–1.83), a lack of incentives (AOR =1.31, 95% CI = 1.04–1.66), and inadequate management support (AOR = 1.19, 95% CI = 1.04–1.66). Health service utilization defects, inappropriate protective equipment utilization, and failure to follow occupational safety commands were identified as challenges. The level of occupational heat exposure and heat-related symptoms was 72.4% (95% CI: 70.2%– 74.8%) and 71.6% (95% CI: 69.3%–74.9%), respectively. The most common heat symptoms were swelling of hands and feet (78%), difficulty breathing (75.9%), dry mouth (77.4%), and heat rash (65.9%). The identified risk factors were a lack of reflective shields (AOR: 2.20, 95% CI: 1.53, 3.17), not-enclosed heat sources (AOR: 1.76, 95% CI: 1.23, 2.51), and inappropriate protective clothing (AOR: 1.58, 95% CI: 1.27, 2.71). During the active sugarcane-crushing period, the level of chronic respiratory health symptoms was 60.6% (95% CI: 59.2–61.9%). The most common respiratory symptoms were wheezing (96.8%), coughing (89.7%), and breathlessness (80.9%). Chronic respiratory symptoms were associated with not wearing proper respiratory protection devices (AOR = 2.08; 95% CI 1.30, 3.08), being exposed to bagasse dust (AOR = 4.79, 95% CI 2.46, 9.33), and the absence of ventilation (AOR = 3.50, 95% CI 2.02, 6.06). From the employer's perspective, the total cost of occupation-related injuries was 22,587,635.32 Ethiopian birr (537,800.84 USD). Indirect and direct costs accounted for 65.86% and 34.14% of the overall expenses, respectively. Long-term absence from work (exp (b) = 0.85), having co- morbid illnesses (exp (b) = 0.85), and the severity (type) of injury (exp (b) = 1.11) were the identified predictors of the total cost variability in the fully adjusted model. Conclusions: Bagasse dust exposure and respiratory health abnormalities were worrying concerns. The lack of dust control technology, not practicing wet spray, and the lack of proper respiratory protective devices increased bagasse dust exposure levels. Not wearing the proper respiratory protection gear, being exposed to bagasse dust, and the absence of ventilation increased the odds of having respiratory abnormalities. Occupational health and safety measures were not utilized effectively as the good practice in the use of OHS measures was shockingly low. Inappropriate protective device provisions, the absence of incentives, and inadequate management support reduced good practices in the use of occupational health and safety measures. The levels of occupational heat exposure and heat-related illnesses were high. The lack of reflective shields, the absence of enclosing extreme heat sources, and inappropriate protective clothing were considerable attributes of heat stress. Our study findings illustrated that employers‘ toll of occupation-related injuries has severe economic implications. Long-term absence from work, co-morbidity, and the severity (type) of injury elevated the total cost variation. Recommendations: The sugar factories and other concerned bodies should focus on mechanical methods to control bagasse dust and excessive heat emissions at their source and strictly implement the potential factors identified in this investigation. Keywords: Economic costs, Physical hazard Exposure, Health Outcomes, Sugar factories, Ethiopia.