Background: Serous cystic neoplasms of the pancreas are regarded as a benign entity with rare malignant potential. Surgical resection is generally considered curative. Objective: To perform the largest single institution review of patients who underwent surgical resection for serous cystic neoplasms of the pancreas. Methods: Between June 1988 and January 2005, 158 patients with serous cystic neoplasms of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Univariate and multivariate models were used to determine factors influencing perioperative morbidity and mortality. Major complications were defined as pancreatic fistula or anastamotic leak, postoperative bleed, retained operative material, or death. Minor complications were defined as wound infection, postoperative obstruction/ileus requiring TPN, delayed gastric emptying, arrhythmia, or other infection. Results: The mean age of the patients was 62.1 years, with 75% being female. The majority of patients were asymptomatic at presentation (63%). Of the 158 patients, 75 underwent distal pancreatectomy, 65 underwent pancreaticoduodenectomy, 9 underwent central pancreatectomy, 5 underwent local resection or enucleation, and 4 underwent total pancreatectomy. Mean tumor diameter was 5.1 cm. Mean operative time was 277.5 minutes. Mean postoperative length of stay was 11 days. One patient was diagnosed with serous cystadenocarcinoma. The remaining 157 patients were diagnosed with benign serous cystadenoma. Two of three patients with locally aggressive benign disease later presented with metastatic disease. Resection margins for all 158 patients were negative for tumor and only 1 (0.6%) showed lymph node involvement. There was one intraoperative death. Major perioperative complications incidence was 18% while minor complications incidence was 33%. Men were significantly more likely to experience minor perioperative complications (OR = 3.74, P = .008) while patients greater than 65 years showed a trend toward fewer major complications (OR = .36, P = .09). Conclusions: Serous cystic neoplasms of the pancreas which are surgically resected are typically seen in asymptomatic women with 5 cm neoplasms and are predominantly benign. Most are resected via either a left or right sided pancreatectomy with low mortality risk, but with notable major or minor morbidity. Cystadenocarcinoma is a rare finding on initial resection of serous cystic neoplasms. However, initial pathology specimens exhibiting benign but locally aggressive neoplasia may indicate an increased likelihood of recurrence or metachronous metastasis.