Introduction. Effective clinical decision-making (CDM) skills are essential for physical therapist practice. The purpose of this study was to compare the effects of virtual reality (VR) patient simulation with those of a traditional standardized patient simulation on the CDM of student physical therapists (SPTs). Review of Literature. Authentic experiential learning opportunities are needed to promote CDM. The effects of VR simulation on the CDM of SPTs are unknown. Subjects. Fifty-nine first-year SPTs participated in this study. Methods. A randomized controlled trial compared the effects of VR with those of standardized patient simulation on several aspects of CDM in 59 first-year students after an upper extremity orthopedic unit. Perceived CDM abilities and metacognitive awareness were assessed before and after allocated instruction. Diagnostic accuracy and diagnostic efficiency were measured during instruction. Student engagement was assessed immediately after instruction and psychomotor skill was assessed 1 week later. Results. Statistically significant within-group differences in CDM were noted after both VR and standardized patient instruction, but no between-group differences were found. Although effect sizes were considered large with either learning experience, the observed experimental effect was greater after a VR experience. No between-group differences were found between metacognitive awareness, diagnostic accuracy, or psychomotor skill assessment. Diagnostic efficiency was statistically significantly greater in the standardized patient condition, while engagement was significantly greater in the VR condition. Discussion and Conclusion. Measures of perceived CDM improved regardless of instructional method; however, the effect size was greater after VR. These findings reveal 2 effective experiential learning options to promote CDM. These results exemplify the normative trajectory of CDM development and recommendations for differentiated curricular instruction. Although resource intensive initially, VR technology appears capable of advancing CDM skills in an efficient manner that may minimize future cost and the faculty facilitation associated with standardized patient instruction.