Background: The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors. Material and Methods: This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study. Results: The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection withTreponema pallidum(HR: 4.02 (95% CI: 1.06–15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59–291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98–0.99)). Conclusions: The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.