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Introduction: Body mass index (BMI) is a simple and cost-effective tool for monitoring the clinical responses of patients living with human immunodeficiency virus (HIV) after antiretroviral therapy (ART) initiation, especially in resource-limited settings where access to laboratory tests are limited. Current evidence on the association between longitudinal BMI variation and clinical outcomes among adults living with HIV receiving ART is essential to inform clinical guidelines. Therefore, this study examines the association between BMI variation and premature mortality in adults living with HIV on ART. Methods: An institution-based retrospective cohort study was conducted among 834 adults living with HIV receiving ART from June 2014 to June 2020 at Debre Markos Comprehensive Specialized Hospital in Northwest Ethiopia. We first identified predictors of mortality and BMI variation using proportional hazards regression and linear mixed models, respectively. Then, the two models were combined to form an advanced joint model to examine the effect of longitudinal BMI variation on mortality. Results: Of the 834 participants, 49 (5.9%) died, with a mortality rate of 4.1 (95% CI 3.1, 5.4) per 100 person-years. A unit increase in BMI after ART initiation corresponded to an 18% reduction in mortality risk. Patients taking tuberculosis preventive therapy (TPT), mild clinical disease stage, and changing ART regimens were at lower risk of death. However, patients with ambulatory/bedridden functional status were at higher risk of death. Regarding BMI variation over time, patients presenting with opportunistic infections (OIs), underweight patients, patients who started a Dolutegravir (DGT)-based ART regimen, and those with severe immunodeficiency had a higher BMI increase over time. However, patients from rural areas and overweight/obese patients experienced a lower BMI increase over time. Conclusion: BMI improvement after ART initiation was strongly associated with a lower mortality risk, regardless of BMI category. This finding implies that BMI may be used as a better predictor tool for death risk in adults living with HIV in Ethiopia. Additionally, patients who took a DGT-based ART regimen had a higher BMI increase rate over time, which aligns with possible positive effects, such as weight gain, of the DGT-based ART regimen in developing countries. [ABSTRACT FROM AUTHOR]