BACKGROUND: Bladder cancer is a disease of the older adult, and management of comorbid conditions requiring anticoagulation (AC) or antiplatelet agents (APA) around the time of radical cystectomy (RC) is a frequent clinical challenge. It is estimated that 10% of adult surgical patients are on chronic anticoagulation medications, and considerations surrounding the perioperative disruption, resumption, and modification or substitution of AC and APA in patients undergoing radical cystectomy are critical for the practicing urologist. METHODS: In our report, we performed a comprehensive literature review using PubMed to evaluate all available studies from 1950 to present. Additionally, we reviewed current multidisciplinary guideline papers from the American College of Surgeons, American College of Cardiology, and CHEST Society regarding perioperative management of anticoagulation and antiplatelet agents. RESULTS: Our keyword search yielded 35 articles from 1950 to 2019. We identified 16 studies pertaining specifically to evaluation and perioperative management of anticoagulation in patient undergoing RC. Many of the recommendations in this realm are informed by trial data outside the RC population in the general surgical population or general adult population. Current guidelines from the American College of Surgeons, American College of Cardiology/American Heart Association, and CHEST Society inform our recommendations heavily and are summarized in Table 1. CONCLUSIONS: Radical cystectomy remains both a mainstay of therapy for patients with muscle-invasive bladder cancer and a morbid procedure. Competing risks of perioperative hemorrhage and thromboembolic events make management of anticoagulation and antiplatelet agents an important and modifiable risk factor. Our review of the current literature highlights the knowledge gap that exists in management of these agents in the radical cystectomy patient. A multi-disciplinary approach to management of this clinical challenge remains a mainstay of treatment.