INTRODUCTION: Irrational use of antibiotics includes prescription of incorrect doses, self-medication and treatment of non-bacterial illness. As a direct consequence of irrational antibiotic use, resistance to the commonly available antibiotics has been increasing rapidly. This phenomenon is associated with poorer health outcomes, longer hospitalization, increased cost to both the patient and government, and increased mortality. The aim of this study was to determine the prevalence of, and examine factors associated with, irrational use of antibiotics in the Moshi municipality, Northern Tanzania. METHODS: We conducted a cross-sectional descriptive study between April and May 2017 in the Moshi municipality. Twelve drug outlets, of which five were pharmacies and seven accredited drug dispensing outlets (ADDOs), were selected at random. On exiting these outlets, all adults who had purchased antibiotics were interviewed using structured questionnaires. RESULTS: A total of 152 adults were enrolled in this study. The median (QR) age was 31 years (25-42). The majority, 94 (61.8%), of the participants were female. ADDOs contributed 81 (53.3%) and pharmacies contributed 71 (46.7%) of all participants. Overall, 135 (88.8%) of antibiotic purchases were irrational. The most prevalent form of irrational antibiotic use was non-prescription usage; 116 of the 152 (76.3%) purchases fell in this category. Purchases of the incomplete dosage and purchases for non-bacterial illness were also widespread. Poor knowledge about the use of antibiotics had a significant association with irrational use of antibiotics (aOR=5.1, 95% CI: 1.80-15.15). CONCLUSION: Irrational use of antibiotics is highly prevalent in this population. Non-prescription use of antibiotics is the most prevalent form. Poor knowledge about antibiotic use plays a significant role in irrational antibiotic use. There is a need to review the accessibility of antibiotics in drug outlets.