Introduction Advancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV reaching older age (≥60 years), making this population's health‐related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts. Methods We used data from the ‘Vive+’ study, a cross‐sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12‐item short‐form survey (SF‐12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors. Results Of the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 interquartile range {IQR} 46.0–58.1 vs. 46.43 IQR 42.5–52.7, p < 0.001) but a similar MCS (median 56.0 IQR 49.34–64.7 vs. 57.0 IQR 48.9–66.3, p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (β correlation factor β −0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (β 0.61 and β −0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years. Conclusion Depressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.