The aim of this study was to determine whether highly active antiretroviral therapy (HAART) is associated with the prevalence of oral lesions in HIV-positive patients. This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was conducted in seven electronic databases (PubMed, Scopus, SciELO, LILACS, Embase, Web of Science, and OpenGrey), without restriction on publication period or language. Studies that showed the prevalence of oral lesions manifested in adult HIV-positive patients, subjected or not to HAART, were selected. The meta-analysis estimate of relative risk was calculated using the Mantel-Haenszel method and DerSimonian and Laird estimator to determine the variance between studies in the random-effects model. The meta-analysis showed significant results in favour of the group on HAART, with lower prevalence for angular cheilitis, erythematous candidiasis, oral herpes, pseudomembranous candidiasis, Kaposi sarcoma, and oral hairy leukoplakia. The prevalence of oral mucosal hyperpigmentation was higher in patients on HAART. These results suggest that the prevalence of oral lesions in HIV-positive patients is lower for those on HAART, which might occur because of the improvement in immunity provided by the therapy.