Background: We have conducted randomized three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel plus CF (DCF) versus radiation with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer, which is on-follow-up for primary analysis planned in 2023 (JCOG 1109). This study aimed to evaluate the influence of preoperative therapies on perioperative complications and risk factors for perioperative complications after three-arm preoperative therapies. Methods: Patients with potentially resectable advanced thoracic esophageal cancer were randomly assigned to three preoperative therapies and followed by open or thoracoscopic esophagectomy with regional lymphadenectomy. Clinical data, surgical results, and perioperative complications in the patients received DCF and CF-RT were compared with those in the patients received CF. Univariate and multivariate analyses were performed to explore the risk factors of perioperative complications. Results: Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200). Of 589 eligible patients, 546 patients underwent surgery (185/183/178). Patients` characteristics were not different between arms. Median number of harvested lymph node in patients received CF-RT was significantly lower than that in patients received CF (49 vs. 58; P< 0.0001). Incidence of ≥ Grade 2 perioperative complications in patients received DCF was lower than that in patients received CF (44.8% vs. 56.2%; P = 0.036). Incidence of ≥ Grade 2 chylothorax in patients received CF-RT was higher than that in patients received CF (5.1% vs. 1.1%; P = 0.032). Incidence of reoperation and intra-hospital death in patients received DCF and CF-RT did not differ from that in patients received CF. Multivariate analysis showed that operation time (≥ median) and open esophagectomy were independently associated with an increase in ≥ Grade 2 perioperative complications. CF-RT was associated with an increase in occurrence of ≥ Grade 2 chylothorax (Relative Risk 4.84; P = 0.043). Conclusions: Preoperative DCF and CF-RT does not increase the risk of perioperative complications and mortality when compared with standard preoperative CF therapy, but CF-RT increases the risk of chylothorax after esophagectomy for advanced thoracic esophageal cancer.