Objective: To summarize the surgical experience in treatment of periampullary carcinoma by three-dimensional (3D) laparoscopic pancreaticoduodenectomy and its clinical efficacy. Methods: The clinical data of 101 patients with periampullary carcinoma undergoing 3D laparoscopic pancreaticoduodenectomy from January 2014 to March 2017 in Department of Hepatobiliary Surgery of Hunan Provincial People’s Hospital were retrospectively analyzed. Results: In the entire group, the average operative time was 325.7 (220–575) min and intraoperative blood loss was 175.9 (100–550) mL; postoperative complications included pancreatic fistula in 23 patients (22.8%) which were classified as biochemical fistula in 17 cases (16.8%), grade B pancreatic fistula in 5 cases (5.0%) and grade C pancreatic fistula in 1 case (1.0%), intra-abdominal bleeding in 7 patients (6.9%), bile leakage in 2 cases (2.0%), delayed gastric emptying in 4 cases (4.0%), intra-abdominal infection in 6 cases (5.9%), pulmonary infection in 3 cases (3.0%) and intestinal obstruction in 2 cases (2.0%); grade 3 complications according to Clavien classification were found in 9 patients (8.9%), of whom 3 cases required a repeated operation, and the 30-day in-hospital death occurred in one patient (1.0%). The average length of postoperative hospital stay was 14.8 (8–29) d. Postoperative pathological data showed that 27 patients (26.7%) had distal common bile duct cancer, 23 patients (22.8%) had ampullary carcinoma, 39 patients (38.6%) had duodenal papillary carcinoma, and 12 patients (11.9%) pancreatic ductal adenocarcinoma; the average tumor diameter was (2.3±1.3) cm, R0 resection rate was 95.0%, and the number of removed lymph nodes was 16.7±4.2, with the number of positive lymph nodes of 1.3±1.1. Conclusion: 3D laparoscopic pancreaticoduodenectomy is safe and effective in treatment of periampullary carcinoma, with a favourable short-term outcome.