Objective To summarize our clinical experience on robot-assisted laparoscopic radical cystectomy combined with orthotopic ileal neobladder in treating bladder cancer, and to evaluate its efficacy and safety. Methods The clinical data of bladder cancer patients, who underwent robot-assisted radical cystectomy combined with orthotopic ileal neobladder from Jan. 2019 to Dec. 2019, were retrospectively analyzed. All the 22 cases were males, aged 32-71 years, with a median age of 63 years. The perioperative data such as operation approach, operation time, extubation time and complications, postoperative pathological results, and the follow-up data such as tumor control and urinary continence were all recorded. Results The operation was successfully performed in all the 22 patients, with no conversion to open surgery. Four cases underwent single-site operation, and two cases underwent full-endoscopic orthotopic ileal neobladder. The operation time was 320-600 min (mean [420±36] min) and the intraoperative blood loss was 100-400 mL (mean [150±17] mL) in the patients, with no blood transfusion during the perioperative period. After surgery, the patients resumed ambulation 1-2 days (median 2 days), recovered bowel function 1-3 days (median 2 days), removed the negative pressure drainage 5-21 days (median 10 days), and removed the urinary catheter 10-25 days (median 14 days) postoperatively. No patients had intestinal complications such as intraoperative intestinal injury or postoperative intestinal obstruction, and there was no incision infection. Neobladder leakage occurred in two cases and recovered spontaneously by prolonged indwelling urinary catheterization. The postoperative pathological results were urothelial carcinoma in all the patients. No tumor recurrence or death occurred during a follow-up of 3-15 months. Twenty patients (90.9%) were satisfied with urinary continence 2 months postoperatively. One patient underwent surgery for internal hernia 4 months postoperatively, and two patients were given intermittent self-catheterization due to dysuria 6 months postoperatively. Conclusion Robot-assisted radical cystectomy combined with orthotopic ileal neobladder is clinically safe and feasible, with satisfactory short-term tumor control and urinary continence. The long-term efficacy needs to be further evaluated by case accumulation and long-term follow-up.