Objectives Cytokine-based immunotherapy (IMT) is a first-line treatment for metastatic renal cell carcinoma (mRCC). Radical nephrectomy and interferon monotherapy were shown to prolong survival of patients with mRCC compared with interferon treatment alone. We prospectively compared the outcome of patients with mRCC who achieved partial remission (PR) under IMT with patients achieving PR under IMT, followed by complete resection of tumor residues. Methods From January 1997 to June 2003, 34 patients with mRCC were treated with IMT and achieved PR. Of these patients, 18 continued IMT until disease progression (group A). In 16 patients with PR, residual tumor tissue was surgically resected (group B). Surgical complications in group B and survival time were evaluated. Results All patients from group B achieved a surgical complete remission (sCR), which is ongoing in 6 of 16 patients. Tumor-related death has occurred in all patients from group A and in 9 of 16 patients from group B. Surgery post-IMT was not associated with intraoperative complications, wound infections, or prolonged postoperative stay. Median overall survival was 50 mo (range: 18–104) versus 58 mo (range: 9–104) for patients in groups A and B, respectively. Conclusions Median survival benefit after IMT and surgery compared with IMT alone was 8 mo for patients who achieved PR. The resection of tumor residues after PR under IMT seems to extend the long-term survival of patients with mRCC and should be attempted when surgically feasible.