Radical cystectomy is a preferred treatment for muscle-invasive bladder cancer. Despite known complications, rapid onset, severe hyperkalemia necessitating abortion of surgery has not been reported. In this case report, a patient with end stage renal disease (ESRD) undergoing attempted cystectomy developed severe intraoperative hyperkalemia and acidosis that led to abortion of surgery and transfer to the medical intensive care unit for emergent hemodialysis. The multifactorial etiology was related to respiratory acidosis, ESRD, patient positioning, clipping of ureters, and body habitus, as well as an idiopathic element. Knowledge of hyperkalemia etiologies can assist in diagnosis and treatment of this serious condition.