Venous thrombotic events (VTEs) may occur at higher rates among patients with HIV; some studies suggest that highly active antiretroviral therapy (HAART) may increase the risk for these potentially life-threatening events. We performed a retrospective study among patients with HIV to evaluate the incidence and risk factors for VTEs during the HAART era. A literature review was performed examining VTEs in the pre- and post-HAART eras. Seventeen (3.7%) of 465 patients with HIV experienced a VTE. The overall incidence rate of deep VTEs among HIV-positive persons was 377 cases per 100,000 person-years, a fourfold higher rate compared to age-matched males in the general population. The median age at VTE was 36 years (range, 27-68). Patients with a thrombosis compared to those without had significantly lower current CD4 (153 versus 520 cells/mm(3), p < 0.001) and nadir (76 versus 276 cells/mm(3), p < 0.001) CD4 counts, higher viral loads (3.6 versus 1.7 log(10) copies per milliliter, p = 0.003), and more likely to have a diagnosis of AIDS (76% versus 32%, p < 0.001); there were no differences in demographics, hyperlipidemia, current use of HAART, the duration of HAART or protease inhibitor (PI) exposure. A review of the literature noted 129 VTE cases; mean age was 40 years, mean CD4 count was 181 cells/mm(3), the majority of patients were not receiving HAART, and the most common risk factor was an ongoing infection. Thrombotic events are occurring among patients with HIV despite their relatively young ages. Advanced HIV disease is a risk factor for development of thromboses, possibly due to an increased inflammatory state or the presence of concurrent comorbidities such as infections. HAART or PI therapy does not appear to play a significant role in the occurrence of VTEs.