Background. The rational use of drugs requires that patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and their community with full information and with the lowest possible cost. If one of these is not met, it is referred to as irrational drug use. Many drugs have been sold or prescribed inappropriately in the world, and a significant part of the world population lacks access to essential medicine. The aim of this study was to assess practice towards rational drug use at Finoteselam and Asirade Zewudie hospitals. Methods. A cross-sectional study design was used for this study, and the study was conducted from October 11 to November 30, 2019. A total of 770 prescriptions were selected as per WHO criteria by using systematic random sampling and reviewed with the help of an observational checklist. The data were entered and processed with SPSS version 25 and evaluated using the WHO criteria. Result. The average number of drugs per prescription was 1.8 and 2.05, antibiotics encountered were 77.7% and 72.5%, injections encountered were 5.97% and 7.01%, percentage of drugs prescribed by generic names was 97% and 93.4%, counseling time was 1.6 minutes and 2.25 minutes, and dispensing time was 51.3 seconds and 62.72 seconds at Finoteselam and Asirade Zewudie hospitals, respectively. Conclusion. The majority of WHO core drug use indicators were not met in the two hospitals. The average number of drugs encountered in Asirade Zewudie hospital was slightly higher than the WHO recommended range, whereas the average number of drugs encountered in Finoteselam hospital was exactly equal. The percentage of antibiotics encountered was very high compared with WHO recommendation, but the percentage of injections encountered was below the WHO recommended range and time spent on counseling and dispensing was too short when compared with WHO recommendation. In addition to this, both hospitals had no essential drug list or formulary as well as a key drug list.