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Insulinomas are rare tumors that originate from the islet cells of the pancreas. The purpose of this study was to analyze our experience in patients with insulinoma and present our approach to these patients. Medical records of 67 patients treated at the University of California, San Francisco (UCSF) Medical Center, 56 surgically and 11 medically, from 1954 to 1995 were retrospectively reviewed. Presenting symptoms, physical findings, laboratory data, pre and intraoperative localization studies, operative management, operative success, and post-operative complications were analyzed. Among the entire cohort, there were 11 patients with Multiple Endocrine Neoplasia type I (MEN 1) and 7 patients with multiple tumors. 46 out of 48 patients (96%) having first operations for benign tumors and 5 out of 8 patients (63%) having reoperations for benign tumors were successful, as were 6 out of 12 patients (50%) having operations for islet cell carcinoma. Overall, preoperative localization studies were positive in only 46% of patients and therefore failed to improve our surgical outcome. Careful palpation with intraoperative ultrasonography gave the best localization results. Enucleation of solitary tumors is curative in sporadic cases and gives the lowest complication rate. In patients with MEN 1, subtotal pancreatectomy with enucleation of tumours from the pancreatic head and uncinate process is recommended over simple enucleation because of frequent multiple tumors.