Abstract: Objective To investigate the clinical manifestations, imaging features, pathogenesis and preventive treatment measures of diffuse brain swelling (MBSC) after cranioplasty. Methods The clinical data of a patient with MBSC were retrospectively analyzed. Results The patient was a 38-year-old male with seizures and pupillary changes within a short period of time after cranioplasty, and the cranial CT suggested significant swelling of the left cerebral hemisphere. The patient died within 72 hours postoperatively even after dehydration and antiepileptic treatment. Conclusion As a rare complication after cranioplasty, MBSC mostly has pupillary changes and seizures as the first manifestation, and the disease progresses rapidly, which seriously endangers the patient's life. Preoperative improvement of cranial depression, intraoperative and postoperative avoidance of excessive and rapid loss of cerebrospinal fluid and prevention of sudden changes in intracranial pressure are the keys to prevent the development of MBSC.