Objective Although considered an integral part of treatment for regionally advanced esophageal cancer, there is conflicting literature regarding the effect of neoadjuvant chemoradiotherapy on esophagectomy. The objectives of this study are to examine the effect of neoadjuvant therapy in regard to perioperative parameters, morbidity, and short-term mortality in patients undergoing a minimally invasive Ivor Lewis esophagectomy (MIE). Methods This is a retrospective review of 39 patients undergoing MIE for esophageal cancer during 2007–2010. Results Of the 39 patients, 14 (36%) did not receive neoadjuvant therapy (NCR) and 25 (64%) did receive either chemoradiotherapy or chemotherapy (CR). On comparing NCR vs CR, there was no difference in operative time (361 vs 362 minutes; P = 0.94) or estimated blood loss (233 vs 190 mL; P = 0.06). All patients underwent an R0 resection, and there was no difference in the mean number of lymph nodes harvested (NCR 21.5 vs CR 21.6; P = 0.95). Both groups had mean intensive care unit stay of 1 day (P = 0.7), and there was no difference in length of stay (NCR 7.4 vs CR 8.2 days; P = 0.38). There were no deaths or anastomotic leaks in either group. The incidence of complications in the NCR group was 21% (3/14) while in the CR group was 48% (12/25). Complications were not associated with neoadjuvant therapy [CR vs NCR: odds ratio = 3.44 (0.72–16.38); P = 0.121], even after adjusting for comorbidities and age. Conclusions MIE can be performed safely following neoadjuvant therapy with similar perioperative results, morbidity, and short-term mortality when compared with MIE alone. Longer follow-up is required for oncologic validity.