Patients undergoing laparoscopic-guided radiofrequency ablation (LRFA) for the treatment of a renal mass are commonly prescribed antithrombotic agents for the management of comorbid medical diseases. We retrospectively evaluated the safety of LRFA in this group. From October 2005 to June 2010, 109 patients underwent LRFA. Antithrombotic therapy was prescribed to 52 of these patients. Agents were managed the week of surgery per current practice guidelines from the American College of Chest Physicians. Intraoperatively, patients prescribed at least one antithrombotic agent lost a median of 10 mL of blood, while patients not on an antithrombotic agent also lost 10 mL of blood (P = .828). Both groups had a similar rate of procedure-related complications (intraoperative, P = 1.00; postoperative, P = .673). No patient required a blood transfusion or experienced a postoperative thromboembolic event. In conclusion, when current practice guidelines are followed, LRFA is safe among patients prescribed antithrombotic agents.