INTRODUCTION: Traditionally esophagectomy is associated with considerable morbidity, mortality and lengthy recovery. While often performed on patients with esophageal cancer who have substantial co-morbidities, outcome comparisons are further confounded by the multitude of open and minimally invasive surgical techniques. We report our experience with open esophagectomy (OE) and minimally invasive esophagectomy (MIE) for malignant diseases of the esophagus. METHODS: Using a comprehensive esophageal cancer database we identified patients who underwent either OE or MIE between 1994 and 2008 for esophageal cancer. Clinical and pathologic data were compared using Fisher’s exact, chi-square, and Kaplan Meier estimates where appropriate. RESULTS: We identified 530 patients with a mean age of 64 ± 10 years who underwent either OE (N=443) or MIE (N=87) with a mean follow-up of 21 +/- 24 months. The median operative time was 285 minutes in OE and 235 minutes in MIE (p<0.001). The median EBL in OE was 250 ml and 150 ml in MIE p=0.57. The leak rate was similar between patients undergoing OE (5.1%) and MIE (8.6%) p=0.2. However, there was a higher stricture rate in MIE (22.5%) compared to OE (12.8%) p=0.02. There was also a higher incidence of wound infections (16.1% v/s 5.1%, p=0.001), and aspiration/pneumonia (35.8% v/s 13%, p=0.001) in the MIE group compared to OE. There were no differences in length of ICU (p=0.59), median LOH (OE 10 days, MIE 10 days, p=0.17) or 30-day mortality (OE 3.6%, MIE 7.4%, p=0.12). More patients who underwent MIE received neoadjuvant therapy then those in the OE group (67% v/s 33%, p=0.02). Multivariate analysis confirmed a higher incidence of wound infections (OR = 4.8; 95% CI 2.0-11.4), and aspiration/pneumonias/effusions (OR = 3.7; 95% CI = 1.5-8.8) in patients undergoing MIE after controlling for age, stage, and neo-adjuvant therapy. There were no differences in lymph nodes sampled (OE (8.7) MIE (9.0), p=0.62) or recurrence rate (OE (21.6%) MIE (25.9%), p=0.39) between groups. Overall survival (p=0.32) and disease-free survival (p=0.91) did not differ between the two cohorts. CONCLUSIONS: MIE and OE are both acceptable approaches to malignant diseases of the esophagus with equivalent post-operative and oncologic outcomes. However, theoretical benefits of improved LOH, post-operative complications, and shorter ICU stay are not observed with the MIE approach, however, some of these differences may be explained by difference in approach (transhiatal versus transthoracic).