The sale of foods on the street is a common aspect of lifestyle in many countries and very prominent in Ghana. The street food trade has evolved into a large food sector that provides a means of income for the vendors and reasonably priced food to millions of people from all walks of life. However, the hygienic aspects of vending operations are a major source of concern for food control officers. As a result of this, there is the need to determine the food safety knowledge and practices of these street vendors so that the safety of such food can be guaranteed. This research was therefore carried out to assess the food safety knowledge and practices of street food vendors in Takoradi. The respondents were 10% male and 90% female. The result indicated that the street food vendors had fair knowledge of food safety practices but a large portion (70%) of them had no medical clearance certificate. The health and personal hygiene knowledge in this survey showed that majority of the vendors do not have any knowledge on health and personal hygiene. It is therefore recommended that a policy should be put in place to periodically educate food handlers especially vendors because food safety education should not only be triggered by evidences of visible dirt or unpleasant body odour.