Objective The efficacy and morbidity of thoracoabdominal incision in comparison with flank incision for radical nephrectomy are unknown. This retrospective study was performed to compare the outcome of thoracoabdominal incision versus flank incision for radical nephrectomy in patients with large renal tumors. Methods A questionnaire assessing the time of postoperative pain, use of anodyne and return to daily activities and work was sent to patients who underwent radical nephrectomy through the 11th rib (flank incision, group A, 96 patients) or the 9th to 10th rib (thoracoabdominal incision, group B, 98 patients) from 2003 to 2008 at the Second Xiangya Hospital in Changsha, China. A case retrospective analysis assessing operation time, perioperative hemorrhage volume, size of tumors, success in the treatment of tumor thrombus in renal vein or vena cava, presence of drainage-tube, postoperative analgesia usage and length of stay was done for patients whose questionnaires were returned. Results The length of operation time and the presence of abdominal drainage-tube was shorter in the thoracoabdominal incision group (group B) than in the flank incision group (group A). The perioperative hemorrhage volume in group B was less than that in group A. The mean size of tumors in group A was smaller than that in group B (Plt;0.000 5). The success rate in the treatment of thrombus in renal vein or vena cava in group B was higher than that in group A (Plt;0.05). The length of off-bed time and of hospital stay were similar in both groups. There were no significant differences between the groups in pain severity postoperative day 1, on the day of discharge and 1 month postoperatively (Pgt;0.05). There were no significant differences between the groups in the time from surgery to the complete disappearence of pain, to the discontinuation of pain medication, and to the return to daily activities and work (Pgt;0.05). Conclusion The approach of thoracoabdominal incision provides better exposure. Morbidity is comparable for thoracoabdominal and flank incisions in terms of incisional pain, analgesic requirements after discharge and return to normal activities.