The impact of instructional guidance on learning outcomes in higher biomedical education is subject of intense debate. There is the teacher-centered or traditional way of teaching (TT) and, on the other side, the notion that students learn best under minimal guidance (problem-based learning, PBL). Although the benefits of PBL are well-known, there are aspects susceptible to improvement. Hence, a format merging TT and PBL (hybrid-PBL, h-PBL) may advance education in biomedical sciences. Here, we systematically reviewed studies that employed h-PBL in higher biomedical education compared to TT and/or pure PBL. We found that h-PBL resulted in better overall students’ performance and perception than TT or pure PBL. These findings encourage more research on investigating the pedagogical benefits of h-PBL and posit an eclectic system in which the pedagogical tools from TT and PBL are used cooperatively in the best interest of the education and satisfaction of the students.