The burden of infectious disease is high among kidney transplant recipients because of concomitant immunosuppression. In this study the incidence of infectious-related mortality and associated factors were evaluated. In this registry-based retrospective, longitudinal cohort study, recipients of a first kidney transplant in Australia and New Zealand between 1997 and 2015 were included. Cumulative incidence of infectious-related mortality was estimated using competing risk regression (using noninfectious mortality as a competing risk event), and compared with age-matched, populated-based data using standardized incidence ratios. Among 12,519 patients, (median age 46 years, 63% men, 15% diabetic, 6% Indigenous ethnicity), 2197 (18%) died, of whom 416 (19%) died from infection. The incidence of infection-related mortality during the study period (1997-2015) was 45.8 (95% confidence interval [95% CI], 41.6 to 50.4) per 10,000 patient-years. The incidence of infection-related mortality reduced from 53.1 (95% CI, 45.0 to 62.5) per 10,000 person-years in 1997-2000 to 43.9 (95% CI, 32.5 to 59.1) per 10,000 person-years in 2011-2015 (P<0.001) Compared with the age-matched general population, kidney transplant recipients had a markedly higher risk of infectious-related death (standardized incidence ratio, 7.8; 95% CI, 7.1 to 8.6). Infectious mortality was associated with older age (≥60 years adjusted subdistribution hazard ratio [SHR], 4.16; 95% CI, 2.15 to 8.05; reference 20-30 years), female sex (SHR, 1.62; 95% CI, 1.19 to 2.29), Indigenous ethnicity (SHR, 2.87; 95% CI, 1.84 to 4.46; reference white), earlier transplant era (2011-2015: SHR, 0.39; 95% CI, 0.20 to 0.76; reference 1997-2000), and use of T cell-depleting therapy (SHR, 2.43; 95% CI, 1.36 to 4.33). Live donor transplantation was associated with lower risk of infection-related mortality (SHR, 0.53; 95% CI, 0.37 to 0.76). Infection-related mortality in kidney transplant recipients is significantly higher than the general population, but has reduced over time. Risk factors include older age, female sex, Indigenous ethnicity, T cell-depleting therapy, and deceased donor transplantation. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_08_27_CJN03200319.mp3. Copyright © 2019 by the American Society of Nephrology.