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Background. Schizophrenia is one of the most severe, chronic, and disabling mental disorders found globally. The chronic nature of the illness significantly interferes with functioning and results in a poor quality of life, but little is known about the quality of life among schizophrenia patients, in particular in low-income countries. Therefore, we assessed the quality of life and associated factors among patients with schizophrenia attending Jimma University Medical Center, Southwest Ethiopia. Methods. The hospital-based cross-sectional study design was employed to collect data from 352 study participants using a systematic random sampling technique from June to July 2018. Patients’ sociodemographic characteristic, quality of life, psychopathology, medication adherence, comorbid physical illness, and substance use disorder were assessed. Data entry and analysis were done using EpiData version 3.1 and Statistical Package for the Social Sciences (SPSS) version 21.0, respectively. Variables with a P value < 0.05 in the final multiple regression models were declared to be associated with the outcome variable. The Results. The response rate of the study was 99.7%. The mean (±standard deviation) score of the World Health Organization Quality of Life Assessment Short Version Scale was 74.34±15.83. Positive symptoms, negative symptoms, general psychopathologies, comorbid physical illness, khat use disorder, tobacco use disorder, and medication nonadherence were negatively associated with patient quality of life. However, monthly income was found to be positively associated with quality of life. Conclusion and Recommendation. The mean and standard deviation of the quality of life of people with schizophrenia is found to be 74.34±15.83 in this study. The social relationship domain was found with the lowest mean score. Therefore, priority interventions need to be implemented to improve the social deficits.