Objectives. To analyze the additional impact of retroperitoneal lymphadenectomy on overall and cancer-specific survival (CSS) in patients with primary renal cell carcinoma (RCC) undergoing radical nephrectomy. The benefit of regional lymphadenectomy in patients with primary RCC remains controversial. Methods. Of 33,016 patients diagnosed with primary RCC between 1983 and 1998, a subset of 4453 underwent radical nephrectomy with or without regional lymphadenectomy. The extent of lymphadenectomy was assessed using the number of nodes examined, and the tumor burden was assessed using the number of positive nodes and the ratio of the number of positive nodes to the total number of nodes examined. Associations between CSS and the number of nodes examined, number of positive nodes, and ratio of the number of positive nodes to the total number of nodes examined were assessed. Results. An inverse correlation was found between the likelihood of CSS and the number of nodes examined, particularly for those with regional disease even after controlling for other factors. A correlation was noted between the number of nodes examined and the number of positive nodes. Significant differences in CSS were observed in node-negative patients with regional disease compared with node-positive patients. An increasing nodal burden was associated with worse CSS. Conclusions. More extensive lymphadenectomy does not appear to increase further the probability of CSS in patients undergoing radical nephrectomy for RCC. An increased number of positive nodes, as well as an increasing nodal burden, although associated with a lower likelihood of survival, were not independent predictors of RCC-specific mortality.