Introduction: Pelvic organ prolapse is the implosion of one or more pelvic floor structures, which compromises a woman's overall health, physical, social, and emotional well-being. Although studies have been conducted in Ethiopia on the prevalence and predictors of pelvic organ prolapse, research determining the quality of life among women with pelvic organ prolapse before surgery is limited; specifically, no study was done on the study area. Objective: To assess the quality of life and its associated factors among women with pelvic organ prolapse who attend gynecology clinics at Gurage zone hospitals, Ethiopia 2022. Methods: Facility-based cross-sectional triangulated with the qualitative study was applied from April, 30 to Jun 30, 2022. Systematic random sampling was employed to select 416 women. Interview and chart review based structured questionnaires were applied to collect the data. The collected data were analyzed using Statistical Produte and Service Solution. Binary and multivariable logistic regressions were fitted to assess the association between dependent and independent variables. P-value <0.05 was used to declare the final statistical significance. For the qualitative part, data were collected through in-depth interviews. Obtained data were analyzed thematically by using open code software (version 4.03). Result: The mean (SD) score of quality of life in this study was 53.57 (21.59). The most affected domains were general health perception (mean (SD) score 67.45 29.24). Had no formal education (AOR=1.50, 95% CI: 1.02, 3.12), stage III/IV POP (AOR=2.02, 95% CI: 1.19, 3.60), constipation (AOR=3.51, 95% CI: 2.12, 7.21), urge urinary incontinence (AOR=3.89, 95% CI: 2.32, 6.95), and not did regular physical exercise (AOR=2.18, 95% CI: 1.41, 3.37) were significantly associated with poor quality of life. Qualitative analysis explored factors that affect quality of life such as bulging’, constipation, urinary incontinence, and discomfort during sexual intercourse. Conclusion: More than half of the participants in this study had impaired quality of life. The factor associated with quality of life was had no formal education, stage III/IV, constipation, urge urinary incontinence, and regular physical activity. It is recommended to have access education, counseling regular physical activity, detection, and management of its comorbidity. Keywords: Quality of life, pelvic organ prolapse, Ethiopia