Background: Improved knowledge regarding antimicrobial use in Ghana is needed to reduce antimicrobial resistance (AMR). This includes point prevalence studies (PPSs) in hospitals. Objectives were to: (i) provide baseline data in two hospitals [Keta Municipal Hospital (KMH) and Ghana Police Hospital (GPH)] and identify priorities for improvement; (ii) assess the feasibility of conducting PPSs; and (iii) compare results with other studies. Methods: Standard PPS design using the Global PPS paper forms, subsequently transferred to their template. Training undertaken by the Scottish team. Quality indicators included: rationale for use; stop/review dates; and guideline compliance. Results: Prevalence of antibiotic use was 65.0% in GPH and 82.0% in KMH. Penicillins and other b-lactam antibiotics were the most frequently prescribed in both hospitals, with third-generation cephalosporins mainly used in GPH. Antibiotic treatment was mainly empirical and commonly administered intravenously, duration was generally short with timely oral switching and infections were mainly community acquired. Encouragingly, there was good documentation of the indications for antibiotic use in both hospitals and 50.0%-66.7% guideline compliance (although for many indications no guideline existed). In addition, almost all prescribed antibiotics had stop dates and there were no missed doses. The duration of use for surgical prophylaxis was generally more than 1 day (69.0% in GPH and 77.0% in KMH). Conclusions: These two hospitals were the first in Ghana to use the Global PPS system. We found the PPS was feasible, relatively rapid and achieved with limited training. Targets for improvement identified included reduction of broad-spectrum antibiotics and duration of treatment.