Fistulas are the preferred permanent hemodialysis vascular access but a significant obstacle to increasing their prevalence is the fistula's high "failure to mature" (FTM) rate. This study aimed to (1) identify preoperative clinical characteristics that are predictive of fistula FTM and (2) use these predictive factors to develop and validate a scoring system to stratify the patient's risk for FTM. From a derivation set of 422 patients who had a first fistula created, a prediction rule was created using multivariate stepwise logistic regression. The model was internally validated using split-half cross-validation and bootstrapping techniques. A simple scoring system was derived and externally validated on 445 different, prospective patients who received a new fistula at five large North American dialysis centers. The clinical predictors that were associated with FTM were aged > or =65 yr (odds ratio [OR] 2.23; 95% confidence interval [CI] 1.25 to 3.96), peripheral vascular disease (OR 2.97; 95% CI 1.34 to 6.57), coronary artery disease (OR 2.83; 95% CI 1.60 to 5.00), and white race (OR 0.43; 95% CI 0.24 to 0.75). The resulting scoring system, which was externally validated in 445 patients, had four risk categories for fistula FTM: low (24%), moderate (34%), high (50%), and very high (69%; trend P < 0.0001). A preoperative, clinical prediction rule to determine fistulas that are likely to fail maturation was created and rigorously validated. It was found to be simple and easily reproducible and applied to predictive risk categories. These categories predicted risk of FTM to be 24, 34, 50, and 69% and are dependent on age, coronary artery disease, peripheral vascular disease, and race. The clinical utility of these risk categories in increasing rates of permanent accesses requires further clinical evaluation.