We examined United States Renal Data System registry records for Medicare-insured kidney transplant recipients in 2000–2011 to study the clinical and cost impacts of urinary tract infections (UTI), pneumonia, and sepsis in the first year post-transplant among a contemporary, national cohort. Infections were identified by billing diagnostic codes. Among 60 702 recipients, 45% experienced at least one study infection in the first year post-transplant, including UTI in 32%, pneumonia in 13%, and sepsis in 12%. Older recipient age, female sex, diabetic kidney failure, nonstandard criteria organs, sirolimus-based immunosuppression, and steroids at discharge were associated with increased risk of first-year infections. By time-varying, multivariate Cox regression, all study infections predicted increased first-year mortality, ranging from 41% (aHR 1.41, 95% CI 1.25–1.56) for UTI alone, 6- to 12-fold risk for pneumonia or sepsis alone, to 34-fold risk (aHR 34.38, 95% CI 30.35–38.95) for those with all three infections. Infections also significantly increased first-year costs, from $17 691 (standard error (SE) $591) marginal cost increase for UTI alone, to approximately $40 000–$50 000 (SE $1054–1238) for pneumonia or sepsis alone, to $134 773 (SE $1876) for those with UTI, pneumonia, and sepsis. Clinical and economic impacts persisted in years 2–3 post-transplant. Early infections reflect important targets for management protocols to improve post-transplant outcomes and reduce costs of care.