Introduction: Patients with Crohn’s disease have been considered particularly challenging laparoscopic candidates due to the nature of the disease and the morbidity of aggressive medical treatment. Hence large definitive prospective studies are lacking. The aim of this study was to compare short and long term outcomes of laparoscopic and open surgery in consecutive patients with ileocolonic Crohn’s disease. Methods: Patients were referred to either a laparoscopic or an open surgeon in our group between August 2002 and July 2005 and were prospectively enrolled. Patients and disease-specific characteristics, intraoperative variables, and short and long term postoperative outcome were analyzed. Results: 83 consecutive patients were operated upon and included in the study. 40 laparoscopic assisted and 43 open ileocolonic resections with hand sewn anastomosis were performed. There were six conversions (15%). Eighteen patients in the laparoscopic group (45%) and 17 in the open (40%) underwent additional surgical procedures. There were no differences in age, gender, body mass index, steroid use, parameters of nutrition and inflammation, previous abdominal surgeries and in the Vienna classification for location or behavior of disease between the two groups. Although the estimated operative blood loss was not statistically different, postoperative blood transfusions were administered only to patients in the open group. The operative time was significantly longer in the laparoscopic group, 216 (100-478) vs. 178 minutes (110-380) (p=0.016). However this difference was due to longer duration of the converted cases (273 minutes) included in the laparoscopic group for intent to treat analysis. The length of stay was shorter, 5.3+0.4 vs. 6.7+0.4 days in the laparoscopic group (p<0.05). Using stepwise multiple regression analysis, the use of laparoscopic surgery was significantly associated with a reduction in the length of hospital stay (p<0.05) even after correcting for other variables such as the anatomical site, behavior of disease, age and prior surgeries. Postoperative mortality was nil. Complication rates were similar including one anastomotic leak requiring reoperation in each group. One patient in each group presented during follow-up with small bowel obstruction, treated conservatively. At a median follow-up of 17 months there have been no surgical Crohn’s disease recurrences. Conclusions: Our study shows that minimally invasive surgery leads to a faster recovery without compromising surgical remission. Laparoscopic surgery should be offered to patients with ileocolonic Crohn’s disease as a safe and effective alternative to open surgery.