BACKGROUND: Retaining patients in clinical care is necessary to ensure successful antiretroviral treatment (ART) outcomes. Among patients who discontinue care, some reenter care at a later stage, whereas others are or will be lost from follow-up. We examined risk factors for health care interruptions and loss to follow-up within a cohort receiving ART in Uganda. METHODS: Using a large hospital cohort providing free universal ART and HIV clinical care, we assessed characteristics and risk factors for treatment interruptions, defined as a 12-month absence from care at Mildmay, and loss to follow-up, defined as absence from care greater than 12 months without reengagement in care at Mildmay. We included patients aged 14 years and above. We assessed these outcomes over time using Kaplan-Meier analysis and multivariable regression. RESULTS: Of 6970 eligible patients, 784 (11.2%) had a health care interruption of at least 12 months and 217 (3.1%) were lost to follow-up. Patients experiencing health care interruptions had higher baseline CD4 T-cell counts at ART initiation, defined as ≥ 250 cells per cubic millimeter [odds ratio (OR): 1.29, 95% confidence intervals (CI): 1.11 to 1.50], and lower levels of education (OR: 1.32, 95% CI: 1.09 to 1.61). Adolescents were much more likely to be lost to follow-up (OR: 3.11, 95% CI: 2.23 to 4.34). In contrast, having a partner (OR: 0.22, 95% CI: 0.16 to 0.31) or being sexually active at baseline (OR: 0.40, 95% CI: 0.28 to 0.55) was protective of loss to follow-up. CONCLUSIONS: Within this cohort, long periods of unsupervised health care interruptions were common.