Background: Medication administration error is a failure in the treatment process resulting in potential harm to the patient. Medication errors are the leading causes of mistrust in the healthcare system, inducing corrective therapy and prolonged hospitalization thereby producing extra costs and even death. These errors are most common and can occur through failures in any of the ten rights of medication administration. About 10% of the overall preventable harm to hospitalized patients is attributed to the wrong use of medications. However, there is limited data regarding the magnitude and determinants of medication administration errors both nationally and in the study area in particular. Methods: A multicenter hospital based, cross-sectional study design was employed on a sample of 422 nurses selected by simple random sampling technique. Pre-tested structured questionnaire and observational checklist were used for data collection from March 1-30/2019. The collected data were cleaned, coded and entered into Epi-data version 4.2 and exported to STATA version 14. Binary logistic regression model was considered and those variables with P<0.25 in the bivariable analysis were included in to final model after which statistical significance was declared at P< 0.05 using adjusted odds ratio at 95% confidence interval. The study findings were presented using tables and figures. Multicollinerity was diagnosed using standard error and correlation matrix. Result: From the overall nurses, 239 (57.7%) of them made medication administration error in the last 12 months. Lack of training [AOR=2.20; 95% CI (1.09, 4.46)], unavailability of guideline [AOR=1.65; 95% CI (1.03, 2.79)], poor communication while facing problems [AOR=3.31; 95% CI (2.04, 5.37)], interruption [AOR = 3.37, 95 % CI (2.15, 5.28)] and failure to follow medication administration rights [AOR=1.647; 95% CI (1.00, 2.49)] were significantly associated with medication administration errors. Conclusion and recommendation: Medication administration error was high in Amhara referral hospitals. Therefore, interventions like developing guideline, providing training and developing strategies to minimize distracters should be given much emphasis by different stakeholders to decrease the burden of medication error.