The PISCIS Cohort is a multi-centre, longitudinal, prospective study of HIV infected individuals. Follow up is performed according to published clinical guidelines. The principal objectives of the cohort are to study the natural history of HIV in the era of cART, evaluating the effectiveness of antiretroviral therapy and studying co-infections such as Hepatitis C and Hepatitis B. Included in the Cohort are all HIV patients aged over 16 who were first followed up at one of the fourteen participating hospitals in Catalonia and the Balearic Islands after January 1998, independently of the stage of disease or degree of immunosuppression. Between January 1998 and June 2016, 20,516 HIV seropositive patients were included (157,466 person-years of follow-up). Ethical approval has been granted by the ethics committee of the coordinating centre and confidentiality is assured through adherence to current data protection law. The PISCIS Cohort actively participates in several international cohort collaborations including ART-CC, COHERE and HIV-CAUSAL.