OBJECTIVES: Advances in the treatment of HIV infection have led to significant improvement in clinical outcomes. Little information is available on the long-term impact of HIV therapy on national health care resource utilization in the US. This study is to evaluate recent trends in hospitalization of patients with HIV disease in the US. METHODS: Data from the Health care Cost and Utilization Project 1993-2001 are analyzed. Hospitalizations due to HIV disease were identified using ICD-9 codes 042 and V08 as both principal diagnoses and all listed diagnoses at discharge. National estimates of HIV hospitalizations were computed based on the weights of the survey sampling structure. RESULTS: The incidence of hospitalizations due to HIV disease as a principal diagnosis increased dramatically from 8.9/100,000 person-years in 1993 to 57.1/100,000 person-years in 1995, then declined significantly to 26.1/100,000 person-years in 2001 (P = 0.0012 from regression analysis). Same trend is followed by total annual hospital charges (in 2001 US$) due to HIV disease as the principal diagnosis, increasing from 0.44 Billion in 1993 to $3.8 Billion in 1995 then dropping to $2.1 Billion in 2001, and its percentage of total annual hospital charges from all causes, increasing from 0.11% in 1993 to 0.79% in 1995, and then declining to 0.38% in 2001. However, the incidence of hospitalizations with HIV disease listed in any diagnostic fields and its percentage of total annual hospital charges show a bimodal trend with two peaks in 1994 (126.1/100,000, 1.88%) and 1998 (99.9/100,000, 1.48%), and a nadir in 2001 (79.3/100,000, 1.18%). CONCLUSIONS: These results suggest that the number of hospitalizations and annual hospital charges due to HIV disease as the principal diagnosis has declined since 1995. However, the same declining trend was not observed for hospitalizations listing HIV disease in any diagnostic fields.