Aims: HIV patients are at high risk of subsequent cardiac events after an ACS, while remain unclear if this vulnerability depends from enhanced thrombosis or progression of plaque. Methods and results: All consecutive patients with HIV infection receiving standard (highly active antiretroviral therapy) HAART therapy presenting with ACS in our centers from January 2001 to September 2012 were studied, recording clinical data regarding the cardiac history and HIV treatment, as well details about the coronary intervention procedures. Cardiac death, new myocardial infarction or revascularizations and in-stent thrombosis were recorded as co-primary end points. We enrolled 201 patients, 179 (89%) male with a median age of 53 (47-62) years, 96 (48%) presenting STEMI. After a median of 701 (284-1237) days, 30 (15%) of patients died, 12 (6%) for cardiac reason, 20 (10%) suffered a myocardial infarction, 29 (15%) a subsequent revascularization and 7 (3.8%) a stent thrombosis with an overall incidence of 44 (21.6%) MACE (major adverse cardiac events). Patients that experience MACE did not differ for cardiovascular risk factor or treatment of choice while showed a higher rate of chronic renal failure (9, 20.5% vs 8, 5.4% p=0.002) and multivessel/left main disease at presentation (30, 68.2% vs 70, 47.6% p=0.017). At the multivariable adjustement, the only independent predictor of MACE was the multivessel/left main disease (HR 1.16-5.58; p=0.02) whereas CD4 count <200 cells/mm3 (HR 1.13-11.8; p=0.031) and not being treated with nucleoside-reverse transcriptase inhibitors (HR 2.59-49.72; p=0.001) were respectively independent predictor of new myocardial infarction and cardiac death. No predictors of repeated revascularization were identified. Conclusions: CD4 count and HAART therapy are clinical predictors of subsequent thrombotic events while not seem to influence the progression of plaque that is represented by repeated revascularization.