The incidence of arterial and venous thrombosis in HIV-infected patients is increased compared to healthy controls. In this cross-sectional analysis we measured markers of endothelial cell activation, thrombin generation, fibrinolysis and anticoagulation combined with endogenous thrombin potential (ETP) and activated protein C sensitivity ratio (APCsr) as more global markers. We included 160 consecutive HIV-infected patients with a median age of 46 years (range, 27-77), of whom 92% were male, 74% Caucasian, 11% African American, 9% Hispanic, and 6% Asian. Homosexual contact was the main transmission mode. Seventy percent of patients were using combined antiretroviral therapy (cART). In 83% of patients laboratory markers outside the normal range for a non-HIV-infected population were observed. Significant lower levels of von Willebrand factor (vWF; p = 0.03), factor VIII (p < 0.0001), D-dimer (p = 0.01), and ETP (p = 0.01) were observed in HIV-infected patients on cART compared to patients not on cART. Significant lower levels of protein C (p = 0.05) and free protein S (p < 0.0001), and increased APCsr (p < 0.0001) were found in the HIV-infected patients not on cART. A single association was observed between raised levels of fibrinogen and use of a protease inhibitor (p = 0.002). No significant difference was observed in the percentage of patients with laboratory markers outside the normal range between patients using cART-regimens containing abacavir, stavudine, or didanosine and those with other nucleoside reverse transcriptase inhibitors. Although the prevalence of coagulation abnormalities was lower in HIV-infected patients using cART, a considerable proportion of HIV-infected patients on cART show endothelial cell activation and increased APCsr, suggestive of a persistent procoagulant state.