Individuals with HIV infection are living substantially longer on antiretroviral therapy, but hospitalization rates continue to be relatively high. We do not know how overall or diagnosis-specific hospitalization rates compare between HIV-infected and uninfected individuals or what conditions may drive hospitalization trends. Hospitalization rates among United States Veterans were calculated and stratified by HIV serostatus and principal diagnosis disease category. Because alcohol-related diagnoses (ARD) appeared to have a disproportional effect, we further stratified our calculations by ARD history. A multivariable Cox proportional hazards model was fitted to assess the relative risk of hospitalization controlling for demographic and other comorbidity variables. From 1997 to 2011, 46,428 HIV-infected and 93,997 uninfected patients were followed for 1,497,536 person-years. Overall hospitalization rates decreased among HIV-infected and uninfected patients. However, cardiovascular and renal insufficiency admissions increased for all groups while gastrointestinal and liver, endocrine, neurologic, and non-AIDS cancer admissions increased among those with an alcohol-related diagnosis. After multivariable adjustment, HIV-infected individuals with an ARD had the highest risk of hospitalization (hazard ratio 3.24, 95 % CI 3.00, 3.49) compared to those free of HIV infection and without an ARD. Still, HIV alone also conferred increased risk (HR 2.08, 95 % CI 2.04, 2.13). While decreasing overall, risk of all-cause hospitalization remains higher among HIV-infected than uninfected individuals and is strongly influenced by the presence of an ARD.