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Background Potentially inappropriate medications (PIM) are associated with adverse health outcomes. The use of PIM among persons living with HIV (PLHIV) could be more problematic due to peculiarities such as antiretroviral toxicity and drug-disease interactions. However, PIM among PLHIV continues to receive little attention. Therefore, we aimed to systematically review and estimate the prevalence of PIM among PLHIV. Methods We searched the PubMed, Scopus, and Web of Science databases to identify relevant studies from 1 January 2014 to 30 June 2024. Studies included were peer-reviewed articles that determined PIM prevalence using validated explicit or implicit tools and provided statistical information on the measured outcomes. Systematic, narrative, and literature reviews as well as case studies, commentaries, and editorials were excluded. Risk of bias was assessed using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. Subgroup analysis was performed for the different geographic regions, PIM criteria, age, study period, and median numbers of medicines. Statistical heterogeneity was assessed using the I2 statistic. Sensitivity analyses, publication bias, and cumulative meta-analysis were conducted. Results A total of 13 articles, including 3200 PLHIV, were included for the systematic review, while meta-analysis was conducted using 8 studies comprising 2546 PLHIV. Most of the studies (46%) employed a cross-sectional study design. 11 out of the 13 studies were conducted in Europe. Most studies reported benzodiazepines as the most common PIM among PLHIV, while hypertension and dyslipidaemia were identified as the most frequent comorbidities. Overall, the pooled prevalence of PIM was 44.8% (95% CI, 32%-58%) using a random-effect model. PIM prevalence among PLHIV was higher among those exposed to polypharmacy (59.3%; CI: 48.9% – 68.9%), those aged > 70 years (44.6%; CI: 24.1–67.1), and post-COVID (48.9%; CI: 39%-59%). Conclusion This study suggests that PIM exposure among PLHIV is a budding issue. Findings from this review advocate for mitigating measures against PIM use. Also, this review contributes data on the use of PIM across different cohorts, creating awareness for policymakers and health managers. Review registration PROSPERO – CRD42024529411.