Objective To explore the effect of flipped classroom based on CDIO (conceive, design, implement, operate) approach on critical thinking, self-directed learning ability, theoretical and practical performance, and satisfaction with teaching in nursing students in the operating room. Methods Seventy-six nursing interns were chronologically assigned to a control group or an intervention group of 38, receiving either routine teaching or flipped classroom teaching strategy based on the CDIO model.Self-directed learning ability, critical thinking ability, theoretical and practical performance, and satisfaction with teaching were compared between the two groups after six weeks of the teaching. Results The above-mentioned indicators in the intervention group were significantly higher than those in the control group （P＜0.05 for all）. Conclusion The application of flipped classroom teaching based on CDIO model in the operating room teaching, is beneficial for nursing students to master theoretical knowledge and practical skills, improve their critical thinking ability and self-directed learning ability.