AimThe aim of this study was to evaluate the effect of enhanced reality simulation on nursing students' learning satisfaction and self-confidence and patient care management knowledge and skills regarding postmastectomy care. BackgroundBreast cancer is a common disease with increasing incidence and mastectomy is the treatment of choice. Postmastectomy patient care is a multidimensional and complex process. For various reasons, nursing students today graduate with inadequate clinical skills and do not have experience with many cases. DesignThis quasi-experimental study was conducted using a pretest–posttest design with a nonequivalent control group. MethodsThis study was conducted with fourth-year nursing students (78 students). Students were allocated to each group through a simple random allocation using IBM SPSS Statistics version 24. Research data were collected at the Clinical Simulation Training Center of the university in 2020–2021 academic year. The study group (n=39) learned using a scenario-based learning approach with moulage in a real clinical setting using enhanced reality simulation, while the control group (n=39) learned using the same scenario-based approach with the routine practice adult standard patient care model. The data were collected through the “Student Sociodemographic and Descriptive Characteristics Data Collection Form”, the “Student Satisfaction and Self-Confidence in Learning Scale”, the “Postmastectomy Patient Care Skills Checklist” and the “Pre–Post Knowledge Test on Postmastectomy Patient Care Management”. ResultsAll 78 participants completed the training course. The training significantly increased the Student Satisfaction and Self-Confidence in Learning Scale subdimension scores of both groups (p<0.05). The Postmastectomy Patient Care Management scores of the study group students who received enhanced reality simulation training significantly increased (p<0.05), while there was no significant effect on the scores of the control group students (p>0.05). While most the students in the study group increased their rates of correct answers to Postmastectomy Patient Care Management questions significantly (p<0.05) after the enhanced reality simulation training, the students in the control group showed no significant improvement (p>0.05). The training significantly (p<0.001) increased the mean postmastectomy patient care skills control scores. This increase had a high effect size on the study group. ConclusionEnhanced reality simulation is a learning method that increases nursing students' learning satisfaction and self-confidence and patient care management knowledge and skills regarding postmastectomy care. Learning with enhanced reality simulation is an effective approach for nursing education that improves nursing students' learning satisfaction and self-confidence and patient care management knowledge and skills regarding postmastectomy care.