Objective To explore the early clinical effect of 3D printing external fixed guide combined with video-assisted thoracic surgery (VATS) in the treatment of flail chest, and to provide evidence for the promotion of this technology. Methods Patients with flail chest treated in our hospital from January 2010 to January 2023 were retrospectively selected as the study objects. The trial group was treated with 3D printed external fixation guide combined with VATS, and the control group was treated with open reduction internal fixation. Operation time, intraoperative blood loss, closed thoracic drainage time, thoracic volume recovery, visual analogue scale (VAS) score 1 month after surgery and complications were compared between the two groups. Results A total of 40 patients were included, 20 in each group. In the experimental group, there were 13 males and 7 females, with an average age of 45.7±3.8 years. In the control group, there were 14 males and 6 females, with an average age of 47.3±4.1 years. There was no statistical difference in gender, age, number of rib fractures or VAS between the two groups (P>0.05). The surgery was successful in both groups, the wounds healed in stage Ⅰ, and the pain symptoms were significantly reduced. No postoperative complications occurred in the trial group, while chronic pain occurred in 1 patient, fracture malunion occurred in 1 patient and incision infection occurred in 1 patient in the control group, with a complication rate of 15.0%. Operation time, intraoperative blood loss and closed thoracic drainage time in trial group were lower than those in control group (P<0.05). There was no statistical difference in the recovery of thoracic volume and VAS at 1 month after operation (P>0.05). Conclusion 3D printing external fixation guide combined with VATS in the treatment of flail chest has satisfactory early curative effect, which has the advantages of minimally invasive, high efficiency, rapid recovery and reducing postoperative complications. This method can effectively reconstruct the shape of the chest, restore the volume of the chest.