Introduction Ghana has a partial smoking ban with smoking allowed in designated smoking areas. Studies evaluating smoke-free laws are scarce in sub-Saharan Africa. Evaluation of smoke-free laws is an effective means of measuring progress towards a smoke-free society. This study assessed the level of compliance to the provisions of the current smoke-free policy using air quality measurement for fine particulate matter (PM2.5) in hospitality venues in Ghana. Methods This was a cross-sectional observational study conducted using a structured observational checklist complemented with air quality measurements using Dylos monitors across 152 randomly selected hospitality venues in three large cities in Ghana. Results Smoking was observed in a third of the venues visited. The average indoor (median) PM2.5 concentration was 14.6ug/m3 (range: 5.2-349). PM2.5 concentrations were higher in venues where smoking was observed (28.3 ug/m3) compared to venues where smoking was not observed (12.3 ug/m3) (p<0.001). Hospitality locations in Accra, Ghana’s capital city, had the lowest compliance levels (59.5%) and poorer air quality compared to Kumasi and Tamale. Conclusions The study shows that while smoking and SHS exposure continues in a substantial number of hospitality venues, there is a marked improvement in PM2.5 concentrations as compared to earlier studies in Ghana. There is still a considerable way to go to increase compliance with the law. Efforts are needed to develop an action plan to build upon recent progress in providing smoke-free public spaces in Ghana.