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Background  Though financial and policy level efforts are made to expand antiretroviral treatment (ART) service free of cost, survival outcome of ART program has not been systematically evaluated in Nepal. This study assesses the mortality rates and determinants among adult HIV-infected patients on ART in Far-western region of Nepal.    Methods  This retrospective cohort study included 1024 (51.2% men) HIV-infected patients aged ≥15 years, who started ART between May 15 th  2006 and May 15 th  2011 in five ART sites in the Far-western region, Nepal. Follow-up time was calculated from the date of ART initiation to date of death or censoring (loss to follow-up, transferred out, or 15 November 2011). Mortality rates (per 100 person-years) were calculated. Kaplan-Meier and Cox-regression models were used to estimate survival and explore determinants of mortality.    Results  The median follow-up time was 19.1 months. The crude mortality rate was 6.3 (95% confidence interval (CI) 5.3-7.6) but more than three-times higher in first 3 months after ART initiation (21.9 (95% CI 16.6- 28.8)). About 12% (83% men) of those newly initiated on ART died during follow-up. The independent determinants of mortality were male sex (hazard ratio (HR) 4.55, 95% CI 2.43-8.51), poor baseline performance scale (bedridden <50% of the day during the past month, HR 2.05, 95% CI 1.19-3.52; bedridden >50% of the day during the past month, HR 3.41, 95% CI 1.67-6.98 compared to normal activity), one standard deviation decrease in baseline bodyweight (HR 1.04, 95% CI 1.01-1.07), and poor WHO clinical stage (stage III, HR 2.96, 95% CI 1.31-6.69; stage IV, HR 3.28, 95% CI 1.30-8.29 compared to WHO clinical stage I or II).    Conclusions  High mortality was observed within the first 3 months of ART initiation. Patients with poor baseline clinical characteristics had higher mortality, especially men. Earlier initiation of ART through expanded testing and counselling should be encouraged in HIV-infected patients.