Neurocognitive impairments commonly occur and adversely impact everyday functioning in older adults infected with HIV, but little is known about successful cognitive aging (SCA) and its health-related quality of life (HRQoL) correlates. Seventy younger (≤40 years) and 107 older (≥50 years) HIV+ adults, as well as age-matched seronegative comparison groups of younger (N = 48) and older (N = 77) subjects completed a comprehensive battery of neuropsychological, psychiatric, medical, and HRQoL assessments. SCA was operationalized as the absence of both performance-based neurocognitive deficits and self-reported symptoms (SCA-ANDS) as determined by published normative standards. A stair-step decline in SCA-ANDS was observed in accordance with increasing age and HIV serostatus, with the lowest rates of SCA-ANDS found in the older HIV+ group (19 %). In both younger and older HIV+ adults, SCA-ANDS was strongly related to better mental HRQoL. HIV infection has additive adverse effects on SCA, which may play a unique role in mental well-being among HIV-infected persons across the lifespan.