It has always been a challenging issue to develop complex professional skills accompanied with sufficient professional knowledge and correct judgement. Previous studies have indicated that students have more opportunities for practice in flipped learning contexts. Basically, complex professional skills training is often risky in different real-world applications. Therefore, most medical training lessons are done through case discussions, interpretation of mannequins, and watching videos. Such learning models are, however, not only ineffective, but students fail to solve real problems without sufficient drills. The advanced progress of 3D simulation technology provides good opportunities to solve these problems. Virtual reality (VR) provides simulations for real clinical scenarios, offering medical students the chance to practice standard complex medical skills repeatedly, as well as thinking about and responding to clinical problems in VR, where they can obtain immediate feedback from VR learning systems. Thus, to enhance medical students' complex medical skills, the study proposes a virtual reality-based flipped learning approach. To investigate the effectiveness of the proposed approach, a quasi-experimental design was conducted with two groups in a lumbar puncture course for postgraduate year (PGY) residents of a hospital The experimental group with 39 students was conducted with virtual reality-based flipped learning (VR-FL), while the control group with 37 students was managed by traditional flipped learning (T-FL).