BACKGROUND: There is a dearth of information regarding mpox risk perception and vaccine acceptance among people living with human immunodeficiency virus (HIV), especially in countries with a dual burden of HIV and mpox, such as Nigeria. METHODS: We used an explanatory mixed methods design and structured questionnaires administered to a clinic-based sample of people living with HIV (n=430), followed by in-depth interviews with a purposive subsample (n=20). Data were analysed using binary logistic regression and the framework approach. RESULTS: More than one-third (38.1% [n=164]) of the respondents self-perceived a high risk of mpox and 64.4% (n=277) indicated a willingness to receive the vaccine. Willingness to accept the mpox vaccine was positively associated with male sex, older age, non-Muslim faith, unmarried status, post-secondary education and current civil service employment. The odds of accepting the mpox vaccine was also higher among respondents who perceived mpox as a serious disease (adjusted odds ratio [aOR] 1.41 [95% confidence interval {CI} 1.12 to 2.35]), self-assessed a higher risk (aOR 1.66 [95% CI 1.19 to 3.06]) and were concerned about contracting the disease (aOR 1.78 [95% CI 1.12 to 3.94]). Reasons for hesitancy included anxiety about vaccine-antiretroviral drug interactions, low risk perception, perceived protection from antiretroviral treatment, the newness of the vaccine, mistrust of authorities and pharmaceutical companies and concerns regarding vaccine safety. CONCLUSIONS: Mpox risk perception and vaccine acceptance were suboptimal. Vaccine acceptance was influenced by sociodemographic, perceived susceptibility and health behaviour-related factors. Targeted risk communication will enhance acceptance of mpox vaccination among people living with HIV in Nigeria.