OBJECTIVES: Develop an essential medicines list (EML) in 2000 to improve rational use of medicines and contain costs in Middle East- Palestine. METHODS: We examined effects of the EML in the Palestinian healthcare public sector. We obtained data on prescription patterns for medicines from 3570 prescriptions given during outpatient visits in 17 health care facilities in the West Bank from 1997 to 2003. We analyzed the prescriptions to measure rational use. We modeled indicators of rational use as a function of the EML and 16 health center indicator variables. RESULTS: The EML was effective in shifting all prescribing indicators toward standard values. To improve rational medicine use, treatment protocols for the most common diseases and continuous education for medical staff is required. CONCLUSIONS: Treatment protocols that limit physicians’ prescription choices for the most common diseases are necessary to improve the rational use of medicines in any setting. We found that the prescribing indicators least affected were the number of medicines per encounter and antibiotics as a percent of all medicines prescribed. The most affected indicator was the injectable medicines as a percent of all prescribed medicines. While change in the use of injectable medicines may be related to changes in individual preferences, cultural beliefs and values, most of the patients were aware of the implementation of EML, since their medicines where changed and substituted with less expensive bioequivalent ones.