Background: Renal cell carcinoma (RCC) demonstrates heterogeneous behavior. Approximately 30% to 40% of patients with clinically localized RCC will later metastasize. Current tools are imperfect for predicting who will have distant spread of disease. The utility of the modified Glasgow Prognostic Score (mGPS) calculated from C-reactive protein (CRP) and albumin levels, has been well-studied as a pre-operative predictive tool in patients with various solid organ malignancies, including clear cell renal cell carcinoma. This score has not been used in the post-operative setting, and we hypothesized that mGPS can be a powerful tool to predicting overall survival. Methods: Patients undergoing nephrectomy for clinically localized RCC from 2005 to 2010 were studied. Inclusion criteria required clear cell histology and no nodal or metastatic disease at the time of surgery. Additionally, only patients with post-operative C-reactive protein and albumin recorded were included in the analyses. Demographic and clinico-pathological variables were analyzed as categorical variables with the exception of age and tumor size, which were analyzed as continuous variables. Patients were assigned an mGPS score of 0, 1, or 2 based on post-operative data (0 = CRP ≤ 10 mg/l, 1 = CRP>10 mg/l and 2 = CRP>10 mg/l and albumin<3.5 g/dL). Survival analyses utilized Kaplan-Meier and multivariate Cox regression models. Results: Study criteria were met in 142 patients. Mean age was 59 years and 61% were men. No patients had T4 disease while 25% had T3, 9% had T2, and 66% had T1 disease. A post-operative mGPS of 0, 1, and 2 was assigned to 69%, 13% and 18% of the study population, respectively. Multivariate analysis identified post-operative high mGPS (mGPS = 2) as an independent predictor of overall survival (HR 5.591; CI 95% 1.508, 20.734; p = 0.010). Conclusions: In patients with clinically localized clear cell renal cell carcinoma, post-operative mGPS score is an independent predictor of overall survival. Accordingly, mGPS may be a useful tool to monitor disease progression in this patient population.