The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged <25 years at start of HAART, those aged 50-54, 55-59, 60-64, 65-59, and 70 or older were 32% (aHR: 0.68, 95% CI: 0.52-0.87), 29% (aHR: 0.71, 95% CI: 0.53-0.96), 34% (aHR: 0.66, 95% CI: 0.46-0.95), 39% (aHR: 0.61, 95% CI: 0.37-1.00), and 43% (aHR: 0.57, 95% CI: 0.31-1.04) less likely to experience an IR. The VR was similar across all age groups. Finally, patients aged 50-59 showed a 3-fold increase (aHR: 3.58; 95% CI: 1.07-11.99) in their risk of death compared to those aged <30 years. In HIV infection, patients aged ≥50 years have a poorer immunological response to HAART and a poorer survival. This age could be used to define medically advanced age in HIV-infected people.