Cystectomy with orthotopic bladder replacement is a complex procedure with various complications and should therefore only be performed at experienced centers. Early postoperative complications include perioperative bleeding, paralytic and mechanic ileus, insufficiency of intestinal or urological anastomosis, fistula, and urinary tract infection (UTI). Some of these complications can at least be avoided through standardized perioperative management. Long-term complications include urinary incontinence, urinary retention, ureteric strictures, sexual dysfunction, pelvic organ prolapse, metabolic disorders, malabsorption, and short bowel syndrome. To detect these complications, patients need a close and lifelong follow-up. This chapter summarizes the complications of neobladder reconstruction and how they can be avoided, detected early, and managed.