The advantages of laparoscopic appendectomy (LA) over open appendectomy (OA) are unclear. This study compares the outcomes of LA versus OA. A retrospective study from 1998 to 2008 of patients (18 years or older) with appendicitis was performed from 12 medical centers. Study outcomes included 30-day postoperative morbidity and length of hospitalization (LOH). Overall, 16,512 patients were included in this study (LA=10,075, OA=6437). Male patients (LA=52.9% vs OA=57.3%, P<0.0001) and patients with perforated appendicitis (LA=19.3% vs OA=32.8%, P<0.0001) were more likely to undergo OA. LA for nonperforated appendicitis was associated with a lower wound infection rate (LA=1.9% vs OA=3.1%, P<0.0001) and shorter LOH (LA=1.4±1.2 vs OA=1.7±1.2 days, P<0.0001). Similar results were seen with LA for perforated appendicitis (wound infection: LA=5.0% vs OA=9.1%, P<0.0001; LOH: LA=3.8±2.7 vs OA=5.2±3.0, P<0.0001). Postoperative abscess drainage and readmission rates were similar between LA and OA for both nonperforated and perforated appendicitis. Multivariable analysis demonstrated that LA was associated with lower wound infection (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.5 to 0.7), higher abscess drainage (OR, 1.3; 95% CI, 1.1 to 1.6), and shorter LOH. In conclusion, LA continues to be the preferred operation for appendicitis in adults.