Crohn's disease is characterised by a high incidence of perianastomotic recurrence after ileocolic resection. The influence of the anastomotic configuration on the incidence of reoperation was evaluated in patients undergoing resection for Crohn's disease. In our Institution, from 1993 to 2007, 308 consecutive patients affected by ileocolic Crohn's disease were submitted to 343 ileocolic resections or right colectomies. In 292 cases (85.1%), an antiperistaltic side-to-side (or functional end-to-end) anastomosis was performed, with an 80 mm linear stapler in 190 cases, a 100 mm linear stapler in 79, and a hand-sewn anastomosis in 23. The other hand-sewn anastomotic configurations were: 30 (8.8%) side-to-side isoperistaltic, 15 (4.3%) end-to-side and 6 (1.8%) end-to-end. The overall morbidity was 7.3%, with two postoperative deaths (0.6%) with no significant differences between groups. There were 38 overall recurrences (11%). In the side-to-side antiperistaltic group, the rate of recurrence was 8.2%, significantly lower than the recurrence rates observed in the other anastomoses (26.9%, p = 0.002), especially side-to-side isoperistaltic anastomosis (33.3%, p = 0.001). Early recurrences (< 1-year) were 2.6%, without significant differences between groups. There was a higher trend for end-to-end anastomosis (16.6%). In the side-to-side antiperistaltic group the morbidity was higher in the large mechanical anastomoses (100 mm length), but the recurrence rate was lower in this group as compared to the 80 mm anastomoses (1.2% vs. 12.1%, p = 0.006). Our non-randomised study suggests a better trend for the wide side-to-side antiperistaltic technique in terms of recurrence rate. These observations need further investigation with randomised controlled trials to compare the different anastomotic procedures.