Background:Medicine vendors fill the gap created by inadequate skilled professionals required for medicine procurement, storage, and distribution in developing countries.Aim:To evaluate self-medication practice and medicine knowledge among medicine vendors and to determine if a relationship exists between both.Materials and Methods:A descriptive, cross-sectional study was conducted, using a pretested questionnaire on 236 medicine vendors in Jos, Nigeria, sampled through a two-stage stratified design. Data collected were analyzed using the Statistical Package for Social Sciences version 16, and the chi-square test was used to determine the association between variables.Results:Self-medication was common (75.4%) among respondents and was not associated (P>0.05) with any of the demographic characteristics studied. The classes of medicines commonly used by respondents for self-medication were analgesics (31.4%), anti-malarials (22.6%), multivitamins (17.7%), and antibiotics (11.25%). A knowledge assessment test revealed that only 34.3% of the respondents had adequate knowledge. There was no significant (P>0.05) relationship between self-medication practice and medicine knowledge, among the respondents. However, the medicine knowledge scores were significantly (P<0.05) associated with holding a certificate in health sciences, years of experience, and the place of practice of the medicine vendors.Conclusion:The present study demonstrated that self-medication practice was high and inadequate medicine knowledge existed among respondents.