BACKGROUND: Poor knowledge concerning appropriate antibiotic use significantly influences the misuse of antibiotics within the community, especially in developing countries where there are weaker health systems to regulate antibiotic dispensing. Antibiotic misuse leads to antibiotic resistance. This study assessed knowledge of appropriate antibiotic use among buyers in the Moshi municipality, Northern Tanzania. METHODS: We conducted a cross-sectional study in Moshi municipality between April and May 2017. Adults who bought antibiotics at drug outlets were invited to participate in the study. An exit interview was conducted with participants to collect their demographics and assess their knowledge concerning appropriate use of antibiotics. A logistic regression model was performed to determine factors associated with correct knowledge concerning antibiotic use. RESULTS: A total of 152 adults with a median age of 30.5 (IQR 25-42) years, were enrolled in the study. Slightly over half (n = 89, 58.6%), responded that they should stop antibiotics after finishing the dose as directed. Half (n = 77, 50.7%) thought that it was acceptable to share antibiotics with other individuals and over half of respondents (n = 95, 65.1%) thought that they should request the same antibiotics if they had used them to treat a similar illness in the past. Only 38 (25%) had adequate knowledge about the use of antibiotics. Sore throat and flu were respectively identified by 62.5% and 46.1% of respondents as conditions that can be treated with antibiotics. Higher levels of education (aOR = 4.11 95%CI = 1.44-11.71) and having health insurance (aOR = 9.05 95%CI = 3.35-24.45) were associated with better levels of knowledge concerning antibiotic use in various illnesses. CONCLUSION: There is inadequate knowledge concerning the indications for antibiotics and their appropriate usage. Health promotion campaigns are needed to educate the population about appropriate antibiotic use and reduce their irrational use.