BACKGROUND: Non-adherence to prescribed medications is possibly the most common reason for poor treatment outcomes among people with diabetes although its rate is highly variable. Data on the magnitude of medication non-adherence and associated factors are scarce in the study area. This study aimed to assess the rate of non-adherence and associated factors among diabetic patients at Debre Markos Comprehensive Specialized Hospital.METHODS: A cross-sectional study was conducted from June 17 to July 17, 2021. Study participants were selected using a simple random sampling technique. Data were collected with a pre-tested structured questionnaire and entered into SPSS version 25. Logistic regression was utilized to determine predictors of medication non-adherence at a significance level of ≤ 0.05.RESULTS:  A total of 176 study participants were enrolled in the study. About 59% of the study participants had type-2 diabetes mellitus. The prevalence of non-adherence to anti-diabetic medications was found to be 41.5%. Male sex, rural residence, being divorced, being merchant, self- or family-borne medical cost, and presence of comorbidities were significantly associated with increased rate of non-adherence to anti-diabetic medications.CONCLUSION: The prevalence of non-adherence to medications among diabetic patients is significantly high in the study area. Public health measures should be strengthened to decrease non-adherence among diabetic patients.KEYWORDS: Medication, Non-adherence, Diabetes, Debre Markos, Ethiopia