Complications from diabetic foot ulcers often lead to increased patient morbidity. Much debate still ensues concerning surgical versus conservative management of neuropathic diabetic foot ulcerations. The present study assessed and compared the efficacy of metatarsal head resection and medical approach in the treatment of neuropathic diabetic foot ulcers located at the plantar surface of metatarsal heads. In a retrospective cohort study, 24 consecutive neuropathic diabetic foot ulcers in the lower area of the metatarsal heads that had undergone metatarsal head resection were included as the operative group. For the control group, we included 25 similar ulcers that were scheduled for medical therapy. With respect to postoperative complications, wound healing occurred earlier in the operative group, and the recurrence rate was inversely greater in the medical treatment group. Also, the hospitalization rate was significantly greater in the medical treatment group. Overall, the long-term complication rate was lower in the operative than in the medical treatment group. Also, the infection rate was greater in the medical treatment group than in the operative group. Comparing early and late clinical outcomes of metatarsal head resection surgery and medical treatment showed complete superiority for the surgical approach, and metatarsal head resection is more completely cost beneficial than the medical approach.