The objective of this study was to evaluate the impact of unplanned conversion to open esophagectomy during minimally invasive esophagectomy (MIE) on postoperative morbidity and mortality for patients with esophageal cancer, as well as to evaluate the variables that influence the need for conversion. This study was a retrospective analysis of patients with esophageal cancer who underwent open esophagectomy or MIE by either a laparothoracoscopic approach or a robotic approach from 2016 to 2018 by using the esophagectomy-specific American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Poisson regression models were used to analyze 30-day outcomes and risk factors for conversion to open esophagectomy during attempted MIE. A total of 2616 patients were identified. The overall conversion rate for MIE was 6.3%. Compared with completed MIE, patients requiring conversion to open esophagectomy had a significantly increased risk of 30-day mortality (risk ratio, 2.63; 95% confidence interval, 1.03 to 6.69) and experienced a variety of other postoperative complications. Patients requiring conversion to open esophagectomy during MIE also experienced worse perioperative outcomes when compared to patients who underwent planned open esophagectomy. Estimated surgical risk on the basis of the ACS NSQIP Surgical Risk Calculator was the only variable found to be independently associated with conversion from minimally invasive to open esophagectomy (risk ratio, 1.03; 95% confidence interval, 1.01 to 1.04, for each 10% increase in risk score). Unplanned conversion to open esophagectomy during MIE is associated with significantly greater morbidity and a 2.6-fold increased risk of death when compared with both completed MIE and planned open esophagectomy. The ACS NSQIP Surgical Risk Calculator may help identify patients preoperatively who are at higher risk for conversion to open esophagectomy during MIE.