© 2015 European Association of Urology. Background: Previous studies showed the prognostic impact of preoperative levels of neutrophil-to-lymphocyte ratio (NLR), plasma fibrinogen, and serum C-reactive protein (CRP) in surgically treated upper tract urothelial carcinoma; however, few papers have discussed the proper use of these indices. Objective: To investigate whether combinations of these three markers, as a cumulative marker score (CMS), improve the accuracy of prognostic models following radical nephroureterectomy (RNU). Design, setting, and participants: A total of 394 patients from multiple institutions were included. Median follow-up was 30 mo. Intervention: All patients underwent RNU without neoadjuvant chemotherapy. Outcome measurements and statistical analysis: Associated outcomes were assessed using multivariate analysis. The CMS was defined as the number of elevated levels of preoperative NLR, plasma fibrinogen, and serum CRP. Results and limitations: Multivariate analyses revealed that an increasing CMS was independently associated with high rates of disease recurrence, cancer-specific mortality, and all-cause mortality following RNU. Addition of the CMS to a model that included standard clinicopathologic predictors significantly improved predictive accuracy by 2.7% for disease recurrence, 3.9% for cancer-specific mortality, and 4.0% for all-cause mortality, which were the highest among other prognostic models using each marker alone or combinations of two. The study is limited by its retrospective nature. Conclusions: Although the use of each inflammatory marker alone may be as predictive as clinicopathologic indices for prognosis, combinations like CMS can provide more accurate prognostic models following RNU. Patient summary: Elevation of blood-based inflammatory markers may be useful for predicting prognosis because of their low cost and accessibility. Among blood-based indices, we examined the efficacy of preoperative neutrophil-to-lymphocyte ratio, plasma fibrinogen, and serum C-reactive protein levels. Although use of each marker alone provides additional prognostic information, the combination of all three markers would be more predictive than any single marker or combinations of two.