OBJECTIVES: Pharmacists have a remarkable role in rational use of drug by presentation of drug information as patient educator, explanation, assessment and performance of drug orders, contribution in drug selection and utilization as physician consultant, drug utilization review and participation in patient outcomes in ambulatory settings.The aim of this study is to evaluate pharmacists' opinion about the factors affecting rational drug use. METHODS: In a cross sectional survey, questionnaires of the study were completed in Convenient Sampling by pharmacists who had been attended in rational use of drug congress in Tehran. RESULTS: A total of 147 pharmacists were enrolled to the study and the highest priorities in irrational use of drug by pharmacists were revealed including 39% lack of appropriate cooperation and communication between physicians and pharmacists, 34% pharmacists' low tariff and economic issues, 45% lack of public knowledge about drug use and 15.8% lack of regulations.  CONCLUSIONS: Lack of public knowledge and awareness about appropriate use of medicines was found the most important factor in promoting irrationality in drug use. Dissemination of rational use of drug ideas, compiling of diverse strategies in education, management, regulation and finance can be very efficient due to a strong relationship between drug policies and performance of regulations and supervisions as well as drug services methods.