OBJECTIVES: To identify the prevalence and associated factors of anxiety in people living with HIV/AIDS in a tertiary centre in Ghana. DESIGN: The study employed a cross-sectional design. SETTING: The study was conducted in the outpatient HIV clinic of a tertiary hospital. PARTICIPANTS: Participants were adult PLWHA receiving OPD care, including those established on combined antiretroviral therapy (cART) and newer patients who were not on cART. Four hundred ninety-five participants aged ≥30 years were consecutively enrolled on the study. INTERVENTIONS: Demographic and clinical data were collected using standard questionnaires and patient files. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression analysis was done to identify associated factors. MAIN OUTCOME MEASURE: Proportion of PLWHA who had HADS score of ≥8. RESULTS: Overall prevalence of anxiety was 61.0% (95%CI: 56.6 - 65.3), with no significant difference between recently diagnosed (≤ 6 months, 64.3%) and those with established diagnoses (>6 months, 59.1%). Urban residence (aOR: 1.67, 95%CI: 1.12 - 2.51), alcohol use (aOR: 1.64, 95%CI: 1.13 - 2.38) and depression (aOR: 13.62, 95%CI: 7.91 - 23.45) were independently associated with anxiety. CONCLUSION: In this sample, 6 in 10 Ghanaian PLWHA had evidence of anxiety. Liaison with the national mental health service for more comprehensive and integrated care and further research into the mental health of PLWHA is recommended to reduce this high burden of anxiety. FUNDING: This study was funded by a grant from the National Institutes of Health Fogarty International Center (R21 TW010479).