Before caring for patients, video instruction is commonly used for undergraduate medical students, and 360° virtual reality (VR) videos have gained increasing interest in clinical medical education. Therefore, the effect of immersive 360° VR video learning compared with two-dimensional (2D) VR video learning in clinical skills acquisition should be evaluated. This randomized, intervention-controlled clinical trial was aimed to assess whether immersive 360° VR video improves undergraduate medical students' learning effectiveness and reduces the cognitive load in history taking and physical examination (H&P) training. From May 1 2018 to October 30 2018, 64 senior undergraduate medical students in a tertiary academic hospital were randomized to receive a 10-min immersive 360° (360° VR video group; n = 32) or 2D VR instructional video (2D VR video group; n = 32), including essential knowledge and competency of H&P. The demographic characteristics of the two groups were comparable for age, sex, and cognitive style. The total procedure skill score, physical examination score, learner’s satisfaction score, and total cognitive load in the 360° VR video group were significantly higher than those in the 2D VR video group (effect sizes [95% confidence interval]: 0.72 [0.21–1.22], 0.63 [0.12–1.13], 0.56 [0.06–1.06], and 0.53 [0.03–1.03], respectively). This study suggested that a10-minute 360° VR video instruction helped undergraduate medical students perform fundamental H&P skills as effectively as 2D VR video. Furthermore, the 360° VR video might result in significantly better procedural metrics of physical examinations with higher learner satisfaction despite the higher cognitive load.