Background : In developing countries, common drugs problems are inefficient drug regulation, lack of availability of essential drugs, and high irrational use of drugs. One of the factors that influence irrational drug use is the lack of education regarding the principle of treatment for prospective doctors. Objective : This study aimed to study the effect of problem-based learning (PBL) methods on competency competencies in pharmacotherapy. Method : This research is a descriptive analysis research using the product moment Pearson correlation. The sampling technique in this study used proportional stratified random sampling. Distributing validated questionnaires to 230 respondents based on problem based learning validation tests and pharmacotherapy competencies. Respondents in this study consisted of 73 students (31.7%), 2016 PSPD students, 81 respondents (35.2%) and 2017 76 respondents (33%). The number of questionnaires distributed was 230 and returned as many as 230. Results : The results of this study indicate that the method of problem based learning has a significant effect on the competency of pharmacotherapy students with a value of p = 0,000 (p <0,005). The value of correlation coefficient in class 2015 r = 0.626, class 2017 r = 0.742 which indicates that the results of this study have a strong relationship, while in force 2016 r = 0.513 indicates that the results of this study have sufficient relationships. The application of problem based learning is able to improve the mastery of material skills and problem solving related to the provision of drug information services by students participating in drug information system courses. Conclusion : There is a relationship between problem based learning on pharmacotherapy competencies in medical students at Muhammadiyah University of Yogyakarta.