Background The adaptation process for first-year medical students is an important problem because it significantly affects educational activities. The previous study showed that 63% of students had difficulties adapting to the learning process in their first year at medical school. Therefore, students need the most suitable learning style to support the educational process, such as Problem-based learning (PBL). This method can improve critical thinking skills, problem-solving and self-directed learning. Although PBL has been adopted in medical education, the effectiveness of PBL in first-year medical students is still not yet clear. The purpose of this meta-analysis is to verify whether the PBL approach has a positive effect in improving knowledge, problem-solving and self-directed learning in first-year medical students compared with the conventional method. Methods We searched PubMed, ScienceDirect, Cochrane, and Google Scholar databases until June 5, 2021. Search terms included problem-based learning, effectiveness, effectivity, and medical student. We excluded studies with the final-year medical student populations. All analyses in our study were carried out using Review Manager version 5.3 (RevMan Cochrane, London, UK). Result Seven eligible studies (622 patients) were included. The pooled analysis demonstrated no significant difference between PBL with conventional learning method in critical thinking/knowledge assessment (p = 0.29), problem-solving aspect (p = 0.47), and self-directed learning aspect (p = 0.34). Conclusion The present study concluded that the PBL approach in first-year medical students appeared to be ineffective in improving critical thinking/knowledge, problem-solving, and self-directed compared with the conventional teaching method.