Prisoners usually need more comprehensive health and social support than the general population. Due to the growing number of prisoners in Ethiopia and limited access to health service, quality of life is a key concern. Compromised health-related quality of life imposes short and long-term consequences on the prisoners, their families, and the healthcare system. In Ethiopia, there are limited studies that investigate health outcomes and health-related quality of life in this particular population. Therefore, this study aimed to assess the magnitude of health-related quality of life and associated factors among prisoners considering the multidimensional nature of health related quality of life. An institution-based cross-sectional study was conducted on 1,246 prisoners who were enrolled using simple random sampling. The World Health Organization Quality of Life (WHOQoL-BREF-26) and Patient Health Questionnaire (PHQ-9) tools were used to assess the HRQoL and depression among prisoners, respectively. The relationships between exogenous, mediating, and endogenous variables were identified using structural equation modeling. As the mediation of effects were present, then the direct, indirect, and total effects were determined. General fit indices of the final model were acceptable (x2/df = 1.76, p < 0.001, RMSEA = 0.06, TLI = 0.90, CFI = 0.91, and SRMR = 0.06). The mean (standard deviation) score of the overall health related quality of life was 53.25 (15.12). Having an underlying medical condition had negative total effect on health related quality of life while visits in prison had positive total effect. Having income-generating work in prison had only a direct positive effect. Whereas, older age, being married, longer duration of imprisonment, and depression all had only a negative direct effect on one or more domains of quality of life (p<0.05). Inmates in Gondar Prison have very poor and compromised levels of physical and psychological health despite having a modest degree of overall HRQoL. The result of this study is significant for people who work in and research the prison environment because it can assist in recognizing prisoners' health needs and devising treatment procedures that take into consideration physical, psychological, environmental, and social relationship aspects.
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