<p>Virtual Reality (VR) is effective for teaching theoretical knowledge, while manikin-based simulations are essential for hands-on skill development. Mixed Reality (MR), which offers haptic feedback, have the potential to teach both knowledge and practical skills. This study evaluates whether MR-based serious games with an integrated manikin can achieve learning outcomes comparable to the blended use of VR-based serious games and manikin-based training. Thirty-two fourth-semester students from Acıbadem Mehmet Ali Aydınlar University voluntarily participated and were randomly assigned to two groups: the VR + M Group (<i>n</i> = 16), trained with the blend of VR-based serious games and manikin-based simulation, and the MR Group (<i>n</i> = 16), trained with MR-based serious games. All participants completed a pretest before training. The VR + M Group underwent VR training and an exam, followed by manikin-based skills training and a hands-on exam. Their overall performance score was the average of the VR and manikin-based exam scores. The MR Group completed MR training and an MR-based exam. Both groups completed a posttest after training. Post-test scores improved significantly in both groups. A statistically significant difference was observed between the overall exam scores of the two groups, with the MR Group scoring higher on average. MR-based serious gaming, when integrated with manikin interaction, shows strong potential as an alternative training method for simulation-based Basic Life Support training.</p>