Background: The impact of induction chemoradiation therapy on esophageal cancer remains controversial. The purpose of this study was to evaluate the comparative effectiveness of induction chemoradiation therapy on perioperative and postoperative outcomes as well as the effect of downstaging in patients with esophageal cancer. Methods: A retrospective study of a prospectively collected database uncovered 455 consecutive patients undergoing esophagectomies for esophageal cancer between 1999 and 2011 at a high-volume institution. Comparison cohorts were patients treated with induction chemoradiation followed by surgery (n = 180) or surgery only patients (n = 189). Median follow-up was 918 days and was complete in 97%. Propensity score analysis controlled for potential allocation-to-treatment bias and created matched groups. Results: Clinical stage of patients in the study was as follows: stages 0 and I, 29%; stage II, 37%; stage III, 34%. Of the 369 patients, 180 (49%) patients received induction therapy and 53 (29%) achieved pathologic complete response. Induction therapy was associated with an increased need for postoperative transfusion, higher wound infection rate, and need for longer chest tube drainage. Overall, 55% of patients undergoing induction therapy were downstaged. In clinical stage III disease, patients who were downstaged were found to have a 3- and 5-year survival benefit compared with surgery alone (3-year, 51% versus 33%, p = 0.01; and 5-year, 44% versus 33%, p = 0.04). Conclusions: Induction chemoradiation therapy for esophageal cancer is associated with minimal perioperative and postoperative morbidity. Downstaging of clinical stage III patients undergoing induction therapy was associated with a 3- and 5-year survival benefit compared with clinical stage III patients undergoing surgery alone.