Background. Unused medicines are those that are expired, discontinued, deteriorated, and/or not intended for any future use. The aim of this study was to assess the prevalence of unused medicines and predicting factors in households of Awi zone, Amhara regional state, Northwestern Ethiopia. Methods. A community-based cross-sectional study was conducted. A survey of unused medicines was conducted through interviews with representatives of households. The collected data were entered with Epi Data version 3.1 and exported to SPSS version 21 for analysis. Predictors of storage of unused medicines were assessed through binary and multivariable logistic regression methods. A confidence interval of 95% and a P-value of <0.05 were considered to declare statistical significance. Results. Of the total of 507 households surveyed, 70 (13.8%) were found to have unused medicines. These constituted twenty-eight types of unused medicines. Anti-infective medicines were the most commonly unused medicines, 58.9%. People who pay for medicines by themselves, those who lacked knowledge about medicines, and those who did not receive enough counseling about medicines they took were found to be 2.6, 4.8, and 3 times more likely to have unused medicines, respectively. Conclusion. A significant amount of unused medicines was present in the community. Strategies aimed at educating the public regarding the safe disposal of unused medicines and an organized method of collection and disposal of unused medicines in the community need to be introduced.