INTRODUCTION: Minimally invasive esophagectomy has been increasingly accepted to treat esophageal cancer. In Japan, neoadjuvant chemotherapy followed by surgery has become the standard procedure for advanced esophageal cancer. A randomized control study has shown neoadjuvant chemotherapy's survival benefits, but it is unknown whether minimally invasive esophagectomy after chemotherapy is viable. This study investigated the feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy. METHODS: From a database of patients with esophageal cancer, 105 patients who had undergone thoracoscopic esophagectomy with radical lymphadenectomy were analyzed retrospectively. Among them, 51 patients had received neoadjuvant chemotherapy with 5-fluorouracil and cisplatin (NAC group). Their operative outcomes, including operative duration, blood loss, the number of dissected lymph nodes, and postoperative morbidity and mortality, were compared with those of 54 patients who underwent surgery without neoadjuvant chemotherapy (control group). The efficacy of neoadjuvant chemotherapy was also assessed. RESULTS: The operating time in the NAC group was significantly longer than in the control group (543 vs 472 min, P < 0.001), but the blood loss was less (323 vs 528 mL, P < 0.001). Recurrent laryngeal nerve palsy was the most frequently observed complication in both groups (27% vs 32%, P = 0.65). No significant differences were observed in the frequency of postoperative complications. There was no mortality in either group. In the NAC group, 43 patients (84.3%) underwent curative resection, and response of more than two-thirds of the pathological tumor was achieved in 11 patients (21.6%), including complete response in one patient (2.0%). CONCLUSION: Thoracoscopic esophagectomy following neoadjuvant chemotherapy could be safely adopted for patients with advanced esophageal cancer.