Abstract Objectives Transient fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD) remain a challenge. The aim of this study was to assess the risk factors of post‐ESD fever and post‐ESD coagulation syndrome (PECS), focusing on the involvement of immunosuppressive drugs and steroids (IM). Methods This retrospective analysis included 510 patients who underwent colorectal ESD at Okayama University Hospital from 2015 to 2020. The incidence rate, clinical outcome, and factors associated with post‐ESD fever and PECS were investigated. Results Post‐ESD fever and PECS occurred in 63 patients (12.4%) and 43 patients (8.4%), respectively. In multivariate analysis, the American Society of Anesthesiologists Physical Status ≥3, the use of immunosuppressants or prednisolone ≥5mg (IM group), and injury to muscle layer/perforation were significantly associated with post‐ESD fever. In PECS, IM group, tumors located on the right side, treatment time ≥60 min, injury to the muscle layer, and multiple lesions were independent risk factors. Both post‐ESD fever and PECS improved conservatively in the IM group, and no serious complication was observed. Conclusions The use of IM was a risk factor for both post‐ESD fever and PECS. However, there were no serious complications in colorectal ESD for patients taking IM.