Several recent clinical studies have demonstrated that laparoscopic colectomy is safe, feasible, and associated with many short-term benefits compared with open colectomy. It is unknown if outcomes observed in clinical trials can be achieved on a population level. The authors used the Nationwide Inpatient Sample to identify laparoscopic and open elective colon resections performed in the United States for each year from 2000 to 2004. They assessed differences in patient characteristics using demographic information and ICD-9 codes. They then used univariate and multiple logistic regression models to analyze the association between surgical approach and in-hospital morbidity, as well as in-hospital mortality and length of hospital stay. Patients undergoing laparoscopic colectomy tended to be younger (61 years vs 66 years, P < .001) and to have fewer comorbidities (Charlson score of 0 in 58.1% vs 37.0%, P < .001). After adjusting for patient characteristics and comorbidities, laparoscopic colectomy was associated with lower in-hospital mortality (0.6% vs 1.7%, P < .001), lower overall complication rate (32.1% vs 38.2%, P < .001), and shorter median hospital stay (5 vs 7 days, P < .001) compared with open colectomy. Significant benefits were observed in wound problems (0.8% vs 1.44%, P < .001); cardiovascular (12.5% vs 15.1%, P < .001), pulmonary (6.2% vs 8.7%, P < .001), and gastrointestinal (13.7% vs 16.1%, P < .001) morbidity; and reintervention rates (1.33% vs 1.66%, P = .02). Outcome benefits of laparoscopic colectomy previously demonstrated in clinical trials are observed on a population level.