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Background We characterized the extent of antiretroviral therapy (ART) experience and postdischarge mortality among hospitalized HIV-infected adults in Zambia. Methods At a central hospital with an opt-out HIV testing program, we enrolled HIV-infected adults (18+ years) admitted to internal medicine using a population-based sampling frame. Critically ill patients were excluded. Participants underwent a questionnaire regarding their HIV care history and CD4 count and viral load (VL) testing. We followed participants to 3 months after discharge. We analyzed prior awareness of HIV-positive status, antiretroviral therapy (ART) use, and VL suppression (VS; 6 months on ART, 74.4% had VS. The majority (92.5%) were discharged, and by 3 months, 48 (21.7%) had died. Risk of postdischarge mortality increased with decreasing CD4, and there was a trend toward reduced risk in those treated for active tuberculosis. Conclusions Most HIV-related hospitalizations and deaths may now occur among ART-experienced vs -naïve individuals in Zambia. Development and evaluation of inpatient interventions are needed to mitigate the high risk of death in the postdischarge period., In Zambia, 86% of hospitalized HIV-infected adults were antiretroviral therapy–experienced, 50% were virally suppressed, and 71% had advanced HIV disease. Mortality within 3 months of discharge was 20%. Advanced HIV disease interventions should target inpatients in sub-Saharan Africa.