The clinical status and prognosis of patients with human immunodeficiency virus (HIV) infection has dramatically changed in the recent years. Cardiovascular diseases can be related to combined antiretroviral therapy and to the aging of HIV-positive population, resulting in significant mortality and morbidity in those patients. It is crucial to understand whether the HIV-status affects the indications and outcomes of cardiac surgery. A literature search was conducted through electronic databases up to 15 May 2020 following PRISMA guidelines. Variables (i.e. patients characteristics) and endpoints (i.e. postoperative complications) were considered as defined in the original publications. All paper describing post-operative outcomes after cardiac surgery were included. Methodological quality of all included studies was assessed using the Newcastle-Ottawa Scale, the Cochrane Risk of Bias tool and the US Preventive Services Task Force grade. A total of eight studies were included in this systematic review; five studies discussed the outcomes of patients with HIV infection, while three studies compared results based on HIV status. All evidences derived from retrospective observational studies with high variability and poor-to-fair quality. Most patients underwent surgical myocardial revascularization. HIV status is not associated with differences in operative mortality (P = 0.32), postoperative mediastinitis (P = 0.30) or pulmonary infective complications (P = 0.67). Cardiac surgery can be considered safe in HIV-positive patients, and HIV status alone should not be considered as a contraindication for cardiac surgery and should not be considered a risk factor for postoperative mortality or perioperative complications. Further studies are required for patients with AIDS.