Purpose To evaluate bone formation after marsupialization of odontogenic keratocysts (keratocystic odontogenic tumors) of the mandible. Patients and Methods A total of 53 patients with mandibular odontogenic keratocysts underwent marsupialization. Clinical and radiographic examinations were done at 1, 3, and 6 months postoperatively. The bone density of the cyst site was measured on the panoramic radiographs using the Digora. The volume of the cyst was measured by injection of saline solution into the cyst cavity. Student t test and Spearman's rank correlation were used for statistical analysis. Results Healing was uneventful in all patients. The diameter of the cysts was 4.1 to 11.0 cm (average 5.4). The panoramic radiographs showed a continuous increase in bone density of the cystic area, with a 22.42% increase at 1 month, 46.07% at 3 months, and 64.69% at 6 months postoperatively compared with the preoperative values. The decrease in cyst volume was 19.05% at 1 month, 55.62% at 3 months, and 79.67% at 6 months postoperatively. The increase in bone density and decrease in cyst volume were more significant in the first 3 months than in second 3 months ( P < .01). The increase in bone density correlated inversely with the decrease in the cyst volume ( P < .01). Conclusion Bone regeneration can occur more rapidly in large mandibular odontogenic keratocysts after marsupialization with drainage by a cyst plug. After 3 months, secondary enucleation of the cyst can be performed.