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Do apparatuses and eyestrain have effects on learning performances and quality of experience? Materials and Methods: 42 participants played a serious game simulating a job interview with a Samsung Gear VR Head-Mounted Display (HMD) or a computer screen. Participants were randomly assigned to 3 groups: PC, HMD biocular, and HMD stereoscopy (S3D). Participants played the game thrice. Eyestrain was assessed pre- and post-exposure with six optometric measures. Learning performances were obtained in-game. Quality of experience was measured with questionnaires. Results: eyestrain was higher with HMDs than PC based on Punctum Proximum of accommodation but similar between biocular and S3D. Knowledge gain and retention were similar with HMDs and PC based on scores and response time. All groups improved response time but without statistically significant differences between HMDs and PC. Visual discomfort difference was statistically significant between PC and HMDs (biocular and S3D). Flow difference was statistically significant between PC and HMDs (biocular and S3D), with the PC group reporting higher Flow than HMD-S3D. Conclusion: short-term learning is similar between PC and HMDs. Groups initially using HMDs continued improving during long-term learning but without statistically significant difference compared to PC. Eyestrain and visual discomfort were higher with HMDs than PC. Flow was higher with the PC group. Our results show that eyestrain does not seem to decrease learning.