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Context: Coping is a modifiable factor that promotes mental well-being. Among people living with human immunodeficiency virus (HIV), it might affect outcomes such as quality of life (QOL). Objective: This study aims to determine the role of coping strategies as a predictor of QOL among HIV outpatients in a general hospital. Methods: This cross-sectional study involved 200 HIV patients under treatment. Consecutive clinic attendees were surveyed using a sociodemographic questionnaire, the 32-item Coping Strategies Inventory, and the World Health Organization QOL in HIV–BREF scale. Statistical analysis was conducted with a significance level set at 0.05. Results: Respondents, with a mean age of 35.54 (standard deviation = 10.88), were predominantly female (67.5%). After accounting for age and gender, linear regression analysis revealed that engagement coping positively predicted all domains (physical, psychological, independence level, social relationships, environment, and spirituality) of QOL (P < 0.05). Disengagement coping, however, emerged as a predictor solely for the social relationship domain (P < 0.05). Conclusion: Coping is a significant determinant of life quality among HIV patients and should be considered in the holistic treatment of patients.