Objective To study the impact of Charlson's comorbidity index on overall survival following radical and partial nephrectomy performed for renal cell carcinoma (RCC). Methods Patients with primary RCC treated by tumor nephrectomy with at least 1 year of follow-up were included. The outcome parameters assessed were overall survival, impact of surgery on quality of life of patients using Karnofsky's index and correlation of survival with respect to comorbid conditions, using Charlson's index comorbidity score, grade and stage of disease. Results A total of 214 tumor nephrectomies were performed during study period, of which 157 (73%) fulfilling the criteria were included in the final analysis. The mean age at presentation was 57 ± 12 years. The mean Charlson's index was 2.89 ± 2.22. Tumor stages were I-IV in 33, 30, 16 and 21%, respectively. The overall survival was 65% at a mean follow-up of 39 ± 5 months. The mean pre op Karnofsky's index was 79.5 ± 7.13 and at follow-up it was 95.41 ± 10.65 (P<.001). The difference in functional status of patient (Karnofsky's Index) for every stage including Stage-IV was statistically significant (P 0.01). Survival analysis showed a significant differences in overall survival according to stage (P 0.001), grade (P 0.001), size of tumor (P 0.001) and Charlson's index (P = 0.05). Conclusions There was significant improvement in the quality of life, following tumor nephrectomy, even for Stage-IV cancers. Multivariate analysis indicated besides tumor stage, grade, and size of the tumor, Charlson's index has a significant predictive value on overall survival.