Background: Osteoporosis is a condition where bones lose mass and strength. The magnitude of adequate knowledge on osteoporosis prevention ranges from 7% to 85.2%. Insufficient knowledge and negative health belief about a certain health condition places someone at risk of complication. In order to plan for the prevention of osteoporosis, information about people’s health belief and knowledge is necessary. Objective: To assess knowledge, health beliefs, and associated factors towards the prevention of osteoporosis among postmenopausal women in Debre Birhan, Central Ethiopia, 2023. Methods: A community based cross-sectional study design was conducted from March 17/ 2023, to April 17/ 2023 among 501 postmenopausal women. List of participants was obtained from the registration books of health extension workers. A simple random sampling technique was employed to select study participants. Data was collected using interviewer administered questionnaire. Data was analyzed using SPSS 23. Bivariable and multivariable logistic regressions were used to identify predictors of knowledge and health belief towards osteoporosis prevention, and P-value ≤0.05 considered statistically significant. Result: This study showed that 39.5% and 40.7% of participants had adequate knowledge and positive health belief towards osteoporosis prevention respectively. Married [AOR=3.86, 95%CI (1.61, 9.26)], university educated [AOR=5.24, 95%CI (1.63, 16.8)], self history of osteoporosis [AOR=4.09, 95%CI (1.73, 9.73)], family history of osteoporosis [AOR=3.92, 95%CI (1.80, 8.54)], and health care worker as source of information [AOR=3.47, 95%CI (1.81, 6.65)] were significantly associated with knowledge towards prevention of osteoporosis. University level education [AOR=6.42, 95%CI (2.28, 18.08)], being civil servants [AOR=2.58, 95%CI (1.04, 6.37)], self history of osteoporosis [AOR=3.68, 95%CI (1.72, 7.85)], family history of osteoporosis [AOR=2.00, 95%CI (1.03, 3.91)], and health care worker as source of information[AOR=2.14, 95%CI (1.24, 3.68)] were significantly associated with health belief towards osteoporosis prevention. Conclusion: More than half of the participants had an inadequate level of knowledge and negative health belief towards osteoporosis prevention. Key words: Osteoporosis, post menopause, knowledge, health belief, Debre Birhan