A second-generation surveillance system of people infected with human immunodeficiency virus (HIV) has been implemented in Spain. Behavioural and clinical data were collected between 2002 and 2011 through an annual one-day, cross-sectional survey in public hospitals, including all in- and outpatients receiving HIV-related care on the survey day. Mean age increased over time (from 38.7 years in 2002 to 43.8 years in 2011) and 68.4% of the 7,205 subjects were male. The proportion of migrants increased from 6.1% to 15.9%, while people who inject or used to inject drugs (PWID and Ex-PWID) decreased and men who have sex with men (MSM) and heterosexuals increased. Unprotected intercourse at last sex increased among MSM and PWID/Ex-PWID. Patients receiving antiretroviral treatment increased significantly from 76.0% to 88.2% as did those with CD4 T-cell counts ≥350 (from 48.2% to 66.9%) and viral copies <200 (from 47.0% to 85.2%). HIV-infected people with hepatitis C virus RNA decreased from 36.0% in 2004 to 29.9% in 2011, while those with HBsAg remained stable at around 4.4%. Implementation of a low-cost, sustainable system for second-generation surveillance in people living with HIV is feasible. In Spain, the information obtained has helped to define and refine public health policy and document treatment effectiveness.