Background: To date, there has been a very limited number of prospective multicenter trials to verify the benefits of minimally invasive esophagectomy (MIE) such as thoracoscopic esophagectomy for esophageal cancer. In this study, we focused on the comparison of MIE and open esophagectomy (OE) using a Japanese nationwide database. Methods: Patient registration for the National Clinical Database (NCD) commenced in January 2011. It is a nationwide project that is linked to the surgical board certification system in Japan. Propensity score matching was performed to compare the MIE with the OE by use of the 2011-2012 NCD database. Results: Esophagectomy for 9584 patients with thoracic esophageal cancer were categorized into MIE (n = 3589) with OE (n = 5995) in the NCD 2011-2012 database. Propensity score matching created a matched cohort of 3515 pairs of patients with MIE and with OE. The operative time was significantly longer in the MIE group than in the OE group (P < 0.001), whereas blood loss was markedly lesser in the MIE group than in the OE group (P < 0.001). There was no significant differences in overall morbidity between the MIE (42.0%) and OE groups (43.1%). In particular, the incidence of the patients who needed prolonged respiratory ventilation more than 48 hours after surgery was significantly less in the MIE group than the OE group ((8.9% vs 10.9%, P = 0.006). Moreover, the incidence of superficial surgical site infection was significantly less in the MIE group compared with the OE group (6.7% vs 8.1%, P = 0.037). However, the reoperation rate within 30 days was significantly higher in the MIE group than in the OE group (7.0% vs 5.3%, P = 0.004). There were no significant differences in 30-day or operative mortality rates between the MIE and OE groups (30-day mortality: MIE 0.9% vs OE 1.1%,operative mortality: MIE 2.5% vs OE 2.8%). Conclusions: Our results suggest that MIE is comparable with conventional OE in terms of short-term outcome after surgery and is regarded as a desirable surgical option for patients with esophageal cancer although MIE was associated with higher reoperation rates and there were no marked benefits in operative mortality.