Objective To explore the effectiveness of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction in the treatment of head titanium mesh exposure complicated with soft tissue infection. Methods Between January 2015 and December 2021, 13 patients with head titanium mesh exposure complicated with soft tissue infection were admitted. There were 9 males and 4 females with a mean age of 42.9 years (range, 23-64 years). The duration of titanium mesh exposure was 22-609 days (median, 102 days). The wound site located at the frontal part in 3 cases, the parietal part in 1 case, the occipital part in 2 cases, the frontal-parietal part in 1 case, the temporal-parietal part in 4 cases, and the frontotemporal part in 2 cases. The titanium mesh had been taken out in 5 patients before admission, leaving skull defect and shape collapse, with signs of infection. The bacterial culture was positive in 7 cases and negative in 6 cases. The imaging examination revealed that the size of the skull defect ranged from 6 cm×5 cm to 21 cm×17 cm and the scalp defect ranged from 1 cm×1 cm to 15 cm×10 cm. The soft tissue infection did not reach dura in 5 cases, reached dura in 6 cases, and reached frontal sinus in 2 cases. The two-stage surgical protocol was used in all patients. In the first-stage operation, the latissimus dorsi myocutaneous flap was designed to repair the skull and scalp defects after removing the titanium mesh and thorough debridement. The size of muscle flap ranged from 13.5 cm×4.0 cm to 21.0 cm×17.0 cm, and the skin flap ranged from 7.0 cm×4.0 cm to 15.0 cm×10.0 cm. After the flap survived and stabilized, the second-stage operation was performed. The titanium mesh was implanted to reconstruct the skull contour. The size of titanium mesh ranged from 7.0 cm×6.0 cm to 21.5 cm×17.5 cm. The interval between the first- and second-stage operations was 3.7-17.8 months, with an average of 11.4 months. The survival of the skin flap, the appearance of the head, and the presence of re-exposed titanium mesh and infection were observed after operation. Results At the first-stage operation, venous embolism occurred in 1 case, and no obvious abnormality was observed after treatment. All the flaps survived and the incisions healed by first intention. Besides, the incisions of the second-stage operation healed by first intention. All patients were followed up 1-96 months (median, 14 months). During follow-up, no exposure to titanium mesh, infection, or other complications occurred. The appearance satisfaction rate of the patients was 92.31% (11/13). There was no significant difference in the skull contour between the affected side and the healthy side in all patients. Conclusion For the head titanium mesh exposure with soft tissue infection, the application of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction can reduce the risks of implant exposure and infection again by increasing the thickness of the scalp and blood supply, filling the wound cavity, and obtain good effectiveness.