BACKGROUND: Individuals with advanced HIV experience high mortality, especially before and during the first months of antiretroviral therapy (ART). We aimed to identify factors, measurable in routine, primary health clinic-based services, associated with the greatest risk of poor outcome. METHODS: We included all individuals enrolled in the standard-of-care arm of a cluster-randomized trial (TB Fast Track); adults attending participating health clinics with CD4 ≤150 cells/µL and no recent ART were eligible. Associations between baseline exposures and a composite outcome (hospitalization/death) over 6 months were estimated using multivariable Cox regression. RESULTS: Among 1515 individuals (12 clinics), 56% were female, the median age was 36 years, and the median CD4 count was 70 cells/μL. Within 6 months, 89% started ART. The overall rate of hospitalization/death was 32.5 per 100 person-years (218 outcomes/671 person-years). Lower baseline CD4 count (adjusted hazard ratio [aHR], 2.27 for <50 vs 100-150 cells/µL; 95% CI, 1.57-3.27), lower body mass index (aHR, 2.13 for BMI <17 vs ≥25 kg/m2; 95% CI, 1.31-3.45), presence of tuberculosis-related symptoms (aHR, 1.87 for 3-4 symptoms vs none; 95% CI, 1.20-2.93), detectable urine lipoarabinomannan (aHR, 1.97 for 1+ positivity vs negative; 95% CI, 1.37-2.83), and anemia (aHR, 4.42 for severe anemia [hemoglobin <8 g/dL] vs none; 95% CI, CI 2.38-8.21) were strong independent risk factors for hospitalization/death. CONCLUSIONS: Simple measures that can be routinely assessed in primary health care in resource-limited settings identify individuals with advanced HIV at high risk of poor outcomes; these may guide targeted interventions to improve outcomes.