Simulation practices in obstetrics and gynecology (OB-GYN) nursing are used in education, practice, assessment, and the investigation of interventional and behavioral skills related to both routine and emergency conditions. This study was conducted in an OB-GYN nursing course to determine the effect of simulation practices on clinical practice satisfaction, clinical stress, and self-confidence in nursing students. A cluster randomized controlled experimental trial was conducted on 122 students (experimental group, n = 58; control group, n = 64). After theoretical training, all of the students applied six scenarios in the OB-GYN nursing simulation laboratory. The students in the experimental group began clinical practice after simulation training, whereas their peers in the control group began clinical practice without prior simulation training. Data in this study were collected using a personal information form, the Pagana Clinical Stress Questionnaire, a self-confidence scale, and a satisfaction subscale from the Clinical Learning Environment Scale on, respectively, the first day and final day of clinical practice. At the end of the clinical practice, average clinical stress in the control group was higher than that in the experimental group (p = .001). No intergroup difference was found in self-confidence levels (p > .05). For the control group, at posttest, the average satisfaction with the clinical learning environment was higher (p = .046) and the average satisfaction with the clinical learning environment was lower (p = .05). In contrast, no mean pretest-posttest differences were found in clinical stress and self-confidence levels in the experimental group (p > .05). In the control group, no mean pretest-posttest difference was found for the clinical learning environment (p > .05), whereas mean clinical stress (p < .001) and self-confidence (p = .012) levels were higher at posttest (p < .05). The findings of this study indicate that simulation training interventions reduce clinical satisfaction and stress in students but do not influence self-confidence. Nursing educators may provide scenario-based simulation training to students taking OB-GYN courses to enhance their preparedness for clinical practice.