Background: Self-directed learning as a concept that was recently considered by educational institutions in Indonesia. Participants should learn to take learning initiatives, analyze learning needs, formulate learning goals, identify learning resources, select and implement appropriate learning strategies, and be able to evaluate their own learning outcomes. The methods of problem-based learning and non-problem-based learning are equally required in order to achieve good self-directed learning for the trainees. The aim of this study was to investigate differences in self-directed learning for students who were taught PBL and non-PBL methods at Muhammadiyah University in Yogyakarta. Method: The nature of the research in this study is not experimental with analytical observation research designs using a cross-sectional approach with layered random sampling technique with a total sample of 90 students. The instruments used were the Self-Assessment Self-Assessment Scale (SRSSDL) from Fisher Instruments. Test analysis with a simple linear regression test. Results: The results of the study identified the SRSSDL score (p = 0.035) and the GPA score (p = 0.046). This means that there are differences between SDL PBL and non-PBL students. Conclusion: There are SDL differences (self-directed learning) between students who teach PBL and non-PBL methods.