Objective: We undertook a longitudinal study in rural Uganda to understand the association of food insecurity with morbidity and patterns of healthcare utilization among HIV-infected individuals enrolled in an antiretroviral treatment program. Design: Longitudinal cohort study Methods: Participants were enrolled from the Uganda AIDS Rural Treatment Outcomes cohort, and underwent quarterly structured interviews and blood draws. The primary predictor was food insecurity measured by the validated Household Food Insecurity Access Scale. Primary outcomes included: a) Health-related quality of life measured by the validated Medical Outcome Study-HIV Physical Health Summary (PHS); b) Incident self-reported opportunistic infections; c) Number of hospitalizations; and d) Missed clinic visits. To estimate model parameters, we used the method of generalized estimating equations, adjusting for socio-demographic and clinical variables. Explanatory variables were lagged by 3 months to strengthen causal interpretations. Results: Beginning in May 2007, 458 persons were followed for a median of 2.07 years, and 40% were severely food insecure at baseline. Severe food insecurity was associated with worse PHS, opportunistic infections, and increased hospitalizations (results were similar in concurrent and lagged models). Mild/moderate food insecurity was associated with missed clinic visits in concurrent models, while in lagged models, severe food insecurity was associated with reduced odds of missed clinic visits. Conclusions: Based on the negative impact of food insecurity on morbidity and patterns of healthcare utilization among HIV-infected individuals, policies and programs that address food insecurity should be a critical component of HIV treatment programs worldwide.