Objective To explore the effect of escape room teaching pedagogy implemented in first-aid skills training for nurses working in the stomatological outpatient clinics. Methods A total of 108 nurses working in outpatient clinics of a stomatology hospital with 1 to 3 years of experience were randomized into an experimental group and a control group, with 54 in each group. The control group used a traditional method for first-aid training, including 12 h of theoretical teaching and skills training, while the experimental group additionally used the escape room teaching methodology for 4 sessions. Results Compared with the control group, the experimental group had significantly higher test scores of theoretical knowledge and practical skills, higher critical thinking ability and teamwork ability after the training (all P<0.05). Conclusion Escape room methodology can be applied to enhance first-aid knowledge and skills of nurses working in the stomatological outpatient clinics and cultivate their critical thinking ability and teamwork ability.