Minimally invasive esophagectomy (MIE) is accepted for resection of early esophageal cancers. Theoptimal surgical approach for more advanced diseaseisunknown. An evaluation of MIE in patients with advanced tumors having undergone neoadjuvant chemoradiotherapy (nCRT) is presented. A retrospective review of patients with esophageal cancer who underwent MIE from November 2006 to November 2011 was performed In total, 96 consecutive patients underwent MIE for malignancy. Median age was 65 years (range 26 to 88), and 86% were male. Adenocarcinoma represented 87% of patients. Eighty-three percent of patients were staged IIa or higher and 62 (65%) patients received neoadjuvant chemoradiotherapy. Four (6%) patients additionally received intraoperative electron beam radiotherapy. Twenty-six (27%) patients received postoperative adjuvant therapy with 22 (85%) of these havingalso received neoadjuvant chemoradiotherapy. All cases were completed thoraco-laparoscopically except for 2 conversions to mini-laparotomy. Twelve (12%) cervical anastomoses and 84 (88%) thoracic anastomoses were performed. Median operative time was 326 minutes (range 193 to 567) and did not differ significantly between those with and without nCRT. Complete pathologic response was seen in 21 (34%) of the 62 patients receiving neoadjuvant treatment. Major and minor morbidities were experienced in 28% and 38.5% of patients. There were 2 (2%) in-hospital mortalities; 1 each having received or not received neoadjuvant therapy. At median follow-up 24 months (range 3 to 70 months), overall survival was 58% and 55 (57%) patients were alive without recurrence. Minimally invasive esophagectomy is an acceptable surgical therapy for advanced-stage esophageal malignancies after nCRT without evidence for increased morbidity or mortality.