Objective: To investigate the value of application of sleeve anastomosis with single-layer continuous prolene suture in pancreaticojejunostomy. Methods: Using a prospective randomized design, 124 patients scheduled to undergo pancreaticoduodenectomy (PD) from August 2009 to March 2014 were divided into three groups, according to different pancreaticojejunostomy methods that included the conventional end-to-end or end-to-side invagination anastomosis (invagination anastomosis group), mucosa-to-mucosa anastomosis of the pancreatic duct to the jejunum (mucosa-to-mucosa anastomosis group) and sleeve anastomosis with single-layer continuous prolene suture (sleeve anastomosis group). The incidence of pancreatic fistula and other surgical variables among the three groups were compared. Results: The operative time for pancreaticojejunostomy in sleeve anastomosis group was significantly shortened compared with invagination anastomosis group or mucosa-to-mucosa anastomosis group (both P<0.05); the incidence of pancreatic fistula in the entire group was 18.5% (23/124), which in sleeve anastomosis group (4.8%) was significantly lower than that in invagination anastomosis group (29.3%) or mucosa-to-mucosa anastomosis group (22.0%) (both P<0.05); There was no significant difference in incidences of other complications (all P>0.05). Intergroup comparison after stratification by pancreatic duct size and pancreatic texture showed that the incidence of pancreatic fistula in those with pancreatic duct diameter less than 3 mm in sleeve anastomosis group (7.1%) was significantly lower than that in mucosa-to-mucosa anastomosis group (50.0%); the incidence of pancreatic fistula in those with soft pancreatic texture in sleeve anastomosis group (11.8%) was significantly lower than that in either invagination anastomosis group (53.3%) or mucosa-to-mucosa anastomosis group (53.8%) (both P<0.05). Intragroup comparison after stratification by pancreatic duct size and pancreatic texture showed that the incidence of pancreatic fistula in firm pancreatic texture subgroup (15.4%) was significantly lower than that in soft pancreatic texture subgroup (53.3%) in invagination anastomosis group (P<0.05); incidence of pancreatic fistula in large pancreatic duct subgroup (7.4%) was significantly lower than that in small pancreatic duct subgroup (50.0%), and in firm pancreatic texture subgroup (7.1%) was significantly lower than that in soft pancreatic texture subgroup (53.8%) in mucosa-to-mucosa anastomosis group (both P<0.05); there was no significant difference between either subgroups of sleeve anastomosis group (both P>0.05). Conclusion: Sleeve anastomosis with single-layer continuous prolene suture is a safe and convenient procedure, and can reduce the incidence of post-PD pancreatic fistula, especially for those with pancreatic duct diameter less than 3 mm, or soft pancreatic texture.