Background: Craniopharyngioma is a kind of intracranial benign tumor that is primarily treated with surgery. At present, a variety of surgical approaches are used for tumor resection. We have conducted a comparative analysis of the two approaches most used in our department. Methods: The study retrospectively analyzed the clinical data from 65 patients with craniopharyngioma surgically treated by the two approaches mentioned above. Among these patients, 24 were treated by lateral supraorbital (LSO) approach and 41 by standard pterional approach. Indicators including, but not limited to, length of incision, operation time, postoperative pituitary function, urine volume, visual function improvement, and hospitalization were used to compare these two groups of patients. Results: The data shows that there was no significant difference in total tumor resection rate (P=0.54), postoperative visual field improvement (P=0.68) and postoperative function of endocrine. However, the LSO approach significantly reduced the operative incision (P=0.001), shortened the operation time (P=0.001) and operative complexity, while reducing the incidence of postoperative complications (P=0.04). Conclusions: In surgical treatment of craniopharyngioma, LSO approach has similar surgical effect with standard pterional approach, but it can significantly shorten the operation time, reduce surgical trauma and the incidence of complications. Therefore, LSO provides another altative to surgical approach for microsurgical removal of craniopharyngioma.