This study assessed the economics of vegetable marketing in urban and semi-urban markets in the Upper West Region of Ghana to identify differentials in profit margins as well as the constraints marketeers face. Mixed method research design was adopted for the study which involved a survey, focus group discussions, and personal observations. Multi-stage sampling and probability proportional to size sampling techniques were used to select the marketeers. One hundred and ninety-six (196) vegetable marketeers comprising 153 urban and 43 semi-urban marketeers were sampled. Gross margin analysis was used to estimate costs and returns while a profit function was used to estimate net profit of the respondents. The results showed that urban marketeers had higher gross margin and net profit per unit order compared to semi-urban marketeers. The urban vegetable market was more competitive but generally marketeers seemed to rely on increased sales volumes to create profits, with urban marketeers being more able to create higher profits. Sales volume therefore accounted largely for marketeers’ profit margin. Lack of representation, weak support services, and lack of appropriate business skills were among the common problems facing the marketeers. Noncompliance to market regulations and business fluctuations were also identified as challenges to vegetable marketing in the study area. The study concluded that vegetable marketing is a profitable venture with prospects to enhance economic empowerment of vegetable marketeers in the study area.