This study sought to identify and document key issues affecting occupational health and safety among artisans in the informal sector in the Bibiani Municipality of the Western North Region of Ghana. To realize this objective, a descriptive cross-sectional study using the qualitative approach was employed. This was done after an ethical clearance had been obtained from the Ghana Health Service Ethics Committee and prior consent was sought from all participants and managers of the study sites. A total of fifteen artisans participated in the study. The artisans spanned three major categories namely: fabrication, construction, and auto mechanic. A semi-structured interview guide was used to obtain responses from the participants through in-depth interviews. Valuable notes were also made from observations during the interview process. Data from the interview were transcribed, coded, and analyzed thematically. Firstly, most respondents displayed adequate knowledge of the concept of occupational health and safety, especially in the area of hazard identification. Secondly, most of the respondents showed positive attitudes toward occupational health and safety. This was evident in their expressed prioritization of occupational safety among all other factors needed to be productive at work. Thirdly, the artisans exhibited an appreciable level of occupational safety practices. Each respondent used at least one PPE on a regular basis. Finally, it was observed that the emergency preparedness of the respondents in the area of first aid responses and fire outbreak management was inadequate. The findings showed that there is more room for improvement for the artisans in the informal sector with regard to their knowledge, attitudes, and utilization of safe practices. There must be regular training for artisans to help update their knowledge and practices on occupational health and safety issues. The district and municipal authorities together with the Environmental Protection Agency (EPA) must organize such training on a regular basis for artisans. Artisans must be strongly encouraged to join well-organized associations to make such training effective. There must be a national law targeting occupational health and safety issues for workers in the informal sector, with an enforcement regime visible at the local level. This will help improve compliance and minimize the incidents of workplace injuries and ill health.