Objectives: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)‐based COVID‐19 booster vaccination (third dose). Methods: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT‐162b2 or mRNA‐1273 between October 2021 and January 2022. We assessed anti‐spike receptor‐binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID100), and T‐cell response (using interferon‐gamma‐release‐assay [IGRA]) at baseline and quarterly follow‐up visits. Patients with reported COVID‐19 during follow‐up were excluded. Predictors of serological immune response were analyzed using multivariate regression models. Results: Of 84 people living with HIV who received an mRNA‐based booster vaccination, 76 were eligible for analysis. Participants were on effective antiretroviral therapy (ART) and had a median of 670 CD4+cells/μL (interquartile range [IQR] 540–850). Following booster vaccination, median anti‐spike RBD IgG increased by 705.2 binding antibody units per millilitre (BAU/mL) and median VNA titres increased by 1000 ID100 at the follow‐up assessment (median 13 weeks later). Multivariate regression revealed that time since second vaccination was a predictor of stronger serological responses (p < 0.0001). No association was found for other factors, including CD4+ status, choice of mRNA vaccine, or concomitant influenza vaccination. In total, 45 patients (59%) had a reactive baseline IGRA, of whom two lost reactivity during follow‐up. Of 31 patients (41%) with non‐reactive baseline IGRA, 17 (55%) converted to reactive and seven (23%) remained unchanged following booster vaccination. Conclusions: People living with HIV with ≥500 CD4+cells/μL showed favourable immune responses to mRNA‐based COVID‐19 booster vaccination. A longer time (up to 29 weeks) since second vaccination was associated with higher serological responses, whereas choice of mRNA vaccine or concomitant influenza vaccination had no impact. [ABSTRACT FROM AUTHOR]