Abstract: Objective To investigate the effects of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on the level of circulating tumor cells (CTCs) in patients with esophageal cancer (EC). Methods A total of 73 patients with EC undergoing MIE (n=38) or OE (n=35) in our department between October, 2015 and October, 2017 were enrolled, with 10 patients with benign esophagus disease and 10 healthy volunteers as controls. The levels of CTCs in the peripheral blood of the participants were detected using CanPatrolTM technique and analyzed for their association with the operation methods and perioperative complications. Results CTCs were detected in 60.3% (44/73) of the EC patients but in none of the control subjects. CTC level after the surgery was significantly higher than that during the surgery, and CTC level during the surgery was significantly higher than that before surgery (P<0.001). The preoperative and intra-operative CTC levels were not significantly different between MIE and OE groups (P>0.05), but the postoperative CTC level was significantly lower in MIE group than in OE group, and postoperative increment of CTC level (from the preoperative level) was significantly lower in MIE group than in OE group (P<0.001). The total incidence of postoperative complications was significantly lower in MIE group than in OE group (28.9% vs 54.3%, P=0.023), and in both groups, CTC levels in patients with complications were significantly higher than those in patients without complications (P=0.001 and P=0.005 in MIE and OE groups, respectively). Conclusion MIE may help to reduce the number of peripheral blood CTCs early after the operation, and dynamic monitoring CTCs level assists in evaluation of the prognosis of EC patients. CTC level may serve as an indicator for monitoring the prognosis of EC.