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Objectives: To investigate the use of statins and acetylsalicylic acid (ASA) in HIV people in clinical practice. Design: A multicenter, nationwide, prospective cohort study, including 1182 consecutive HIV patients was conducted. Methods: Statin and ASA prescription was evaluated in primary and secondary cardiovascular disease prevention, according to the European AIDS Clinical Society (EACS) guidelines. Results: Followed-up patients (998) were mostly males (70.9%) with a mean age at enrolment of 46.5years (SD 9.5). The mean time of follow-up was 3.3years (SD 0.8). At the last follow-up visit, statins would have been recommended for 31.2% and ASA for 16% by EACS guidelines. Conversely, only 15.6 and 7.6% of patients were on statin and ASA treatment, respectively; only 50.3% of patients treated with statins achieved recommended low-density lipoprotein cholesterol (LDL-c) levels. At the last follow-up visit, agreement between statin therapy and EACS recommendation was 0.58 (95% CI 0.52–0.63). The corresponding figure for ASA therapy was 0.50 (95% CI 0.42–0.58), whereas the agreement for ASA therapy in secondary prevention was 0.59 (95% CI 0.50–0.68). Conclusions: The prescription of statins and ASA in HIV-infected patients remains largely suboptimal, as only about 50% of patients requiring statins and ASA are properly treated. Higher attention on this relevant issue and further investigation are warranted in this at risk population.