Objective To investigate the awareness of rational use of drug (RUD) on medical workers in hospitals of different ranks, the establishment and execution of relevant strategies in hospitals of different ranks, and the main factors affecting RUD on medical workers, so as to provide references for the generalization of RUD. Methods A certain number of different ranks of hospitals in Chengdu and Zigong were randomly selected by the convenience sample method. Medical workers in each hospital were selected through face-to-face interviews with a self-designed questionnaire. Monte Carlo Chi-square analysis was applied on the hospital ranks and formulation of RUD guidelines, and logistic regression analysis was performed on the awareness of RUD knowledge of the respondents. Results Among 700 questionnaires distributed, 672 were retrieved (response rate 96.0%). The numbers of respondents who were familiar with the Pharmaceutical Affairs Councils (PACs) as well as the Pharmacy and Therapeutics Committees (PTCs) were 217 (32.29%) and 83 (12.35%), respectively. The number of respondents who understood the concept of essential medicine was 502 (74.71%). A total of 441 (61.16%) medical workers had been trained on RUD, 199 (29.61%) medical workers denied there were PTCs in their hospitals, and 60.71% of the medical workers mentioned that the use of drug was monitored and controlled with the feedback in their hospitals. The result of logistic regression analysis indicated that the professional title (P=0.038), awareness of essential medicine (Plt;0.001) and participation of RUD training (P=0.008) were the factors influencing the awareness of RUD. Conclusion Both management and education should be executed at the same time to elevate the level of rational use of drug. In order to increase the level of RUD we should complete monitoring institution and improving RUD awareness of workers. Additionally enhancing the rationality of medication should be performed by establishing guidelines of treatment or medication. Improving personal knowledge, scientific information and medication custom should be performed by standardizing regulations, strengthening management, emphasizing education and promoting communication between doctors and patients.