Pneumococcal vaccine is recommended for adults 65 years and older and those younger than 65 years with clinical indications (eg, diabetes, lung/heart disease, kidney failure, and nephrotic syndrome). Its cost-effectiveness in less severe chronic kidney disease (CKD) is uncharacterized. Cost-effectiveness analysis. US adults aged 50 to 64 and 65 to 79 years stratified by CKD risk status: no CKD (estimated glomerular filtration rate≥60mL/min/1.73m2 and urinary albumin-creatinine ratio<30mg/g), CKD with moderate risk, CKD with high risk, and kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2) or nephrotic-range albuminuria (urinary albumin-creatinine ratio≥2,000mg/g). Data sources were the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004, Centers for Disease Control and Prevention, and the Atherosclerosis Risk in Communities (ARIC) Study. Vaccination compared to no vaccination. Incremental cost-effectiveness ratios based on US dollars per quality-adjusted life-year (QALY). Markov model, US health sector perspective, and lifetime horizon. The prevalence of pneumococcal vaccination in NHANES 1999 to 2004 was 56.6% (aged 65-79 years), 28.5% (aged 50-64 years with an indication), and 9.7% (aged 50-64 years without an indication), with similar prevalences across CKD risk status. Pneumococcal vaccination was overall cost-effective (<US $100,000/QALY) for adults aged 65 to 79 years (US $15,000/QALY) and 50 to 64 years (US $38,000/QALY). Among those aged 50 to 64 years, incremental cost-effectiveness ratios were lowest for kidney failure or nephrotic-range albuminuria (US $1,000/QALY), followed by CKD with high risk (US $17,000/QALY), CKD with moderate risk (US $25,000/QALY), and no CKD (US $43,000/QALY). Pneumococcal vaccination was cost-effective among adults aged 50 to 64 years with CKD even when assuming the lowest vaccine efficacy or 50% higher vaccine costs. Some model parameters were based on data from the general population. Analysis did not consider costs associated with kidney disease progression. Uptake of pneumococcal vaccination should be improved in general. Our results also suggest the cost-effectiveness of expanding its indication to younger adults with CKD less severe than kidney failure or nephrotic syndrome.