Background. Kidney disease affects absorption, distribution, metabolism, and excretion of medicines and their metabolites. Therefore, when prescribing medicines for patients with kidney disease, dose adjustment is an accepted standard of practice. Objective. This study aimed to assess medicine dose adjustment practice and associated factors among adult patients with renal impairment admitted to medical wards at Amhara region referral hospitals. Method. Multicenter, institution-based, cross-sectional study was conducted from March 28, 2020, to August 30, 2020. The data was collected by using a pretested interviewer-administered structured questionnaire. Data were entered into Epi-Data version 4.6 and transferred into SPSS version 25 for further data processing and analysis. Descriptive statistics such as frequencies and percentages were computed. Both bivariable and multivariable binary logistic regression analyses were fitted to identify factors associated with dose adjustment practice. A 95% confidence interval and a p value less than 0.05 were used to declare statistical significance. Result. Among 815 medicines’ prescriptions that needed dose adjustment, 417 (51.2%) of them were dosed inappropriately. Number of medicines, number of comorbidities, and being unemployed were significantly associated with inappropriate dose adjustment. Conclusion. Our study revealed that there was a considerable rate of inappropriate dose adjustment in patients with renal impairment. Training for health care providers, use of guidelines, and communication with clinical pharmacists should be encouraged for good prescription practice.