<p><strong>Introduction:</strong> Increasingly, partial nephrectomy has been applied to high-risk disease without evidence that its survival benefits can be extrapolated to this entity. We aimed to compare overall survival after partial vs. radical nephrectomy in patients with high-risk renal cell carcinoma.</p><p><strong>Methods:</strong> Using the National Cancer Data Base, we identified patients who underwent partial or radical nephrectomy for high-risk disease between 2003 and 2006. High-risk disease was defined as the presence of adverse pathological features within the primary tumour, namely high-grade or unfavourable histology, T3 stage, or both. After matching the partial and radical nephrectomy groups<br />based on propensity scores, 1680, 276, and 76 patients with high-grade or unfavourable histology, T3 stage, or both adverse pathologic features, respectively, were available for analysis. Five-year overall survival was compared after partial vs. radical nephrectomy for each high-risk cohort using the Kaplan-Meier and log rank tests.</p><p><strong>Results:</strong> Partial nephrectomy was associated with a statistically significant improvement in five-year overall survival compared to radical nephrectomy for small tumours (median size 3.0 cm; interquartile<br />range 2.1‒4.5 cm) with high-grade or unfavourable histology (87% vs. 81%; p<0.01) or with pT3a stage (82% vs. 71%; p<0.01). For patients concomitantly harbouring both adverse pathologic<br />features, no difference in survival was detected (p=0.21).</p><p><strong>Conclusions:</strong> Partial nephrectomy is associated with survival benefits in patients with adverse pathologic features, suggesting that renal preservation is not only safe, but also potentially beneficial for high-risk disease. Due to inherent selection bias associated with partial nephrectomy use, prospective validation of these findings is needed.</p>