Background Providers need a reliable way to identify patients with chronic kidney disease (CKD) at the highest risk of progression to end-stage renal disease so they can intervene to slow progression and refer patients to nephrology for comanagement. We developed a risk score to predict the 5-year risk of renal replacement therapy (RRT) in patients with stage 3 or 4 CKD. Study Design Retrospective cohort study. Setting & Participants Participants were members of a health maintenance organization and met Kidney Disease Outcomes Quality Initiative criteria for stage 3 or 4 CKD during 1999 or 2000: two estimated glomerular filtration rate values of 15 to 59 mL/min/1.73 m2. Predictor Characteristics collected during routine clinical practice. Outcomes & Measurements We ascertained the onset of RRT (dialysis or kidney transplantation) using the health maintenance organization databases. Cox regression predicted patient risk of RRT and generated a risk scoring system. Results 9,782 patients experienced a 3.3% five-year progression to RRT (95% confidence interval, 2.9 to 3.7). Using 6 characteristics (age, sex, estimated glomerular filtration rate, diabetes, anemia, and hypertension), the risk score discriminated the highest risk patients effectively: 19.0% of patients in the highest risk quintile experienced progression, and 0.2% of patients in the lowest risk quintile experienced progression. The c statistic also showed effective discrimination: 0.89 on a scale of 0.5 to 1.0. Predicted and observed risks agreed within 1.0%—effective calibration. We present a range of predicted risk cutoff values from 1% to 20% and their test properties for decision makers' consideration. Limitations Characteristics were measured without a protocol. Conclusions The risk score can help providers identify patients with CKD at the highest risk of progression to improve referral to nephrology for comanagement. A separate risk score for mortality also is needed.