Hypothesis: The use of kidneys from deceased donors considered at increased infectious risk represents a strategy to increase the donor pool. Design: Single-institution longitudinal observational study. Setting: Tertiary care center. Patients: Fifty patients who gave special informed consent to receive Centers for Disease Control and Prevention high-risk (CDCHR) donor kidneys were followed up by serial testing for viral transmission after transplantation. Nucleic acid testing for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus was performed on all high-risk donors before transplantation. Outcomes of CDCHR kidney recipients were compared with outcomes of non-high-risk (non-HR) kidney recipients. Main Outcome Measures: New viral transmission, graft function, and waiting list time. Results: No recipient seroconversion was detected during a median follow-up period of 11.3 months. Compared with non-HR donors, CDCHR donors were younger (mean [SD] age, 35  vs 43  years, P=.01), fewer were expanded criteria donors (2.0% vs 24.8%, P<.001), and fewer had a terminal creatinine level exceeding 2.5 mg/dL (4.0% vs 8.8%, P=.002). The median creatinine levels at 1 year after transplantation were 1.4 (interquartile range, 1.2-1.7)mg/dL for CDCHR recipients and 1.4 (interquartile range, 1.1-1.9) mg/dL for non-HR recipients (P=.4). Willingness to accept a CDCHR kidney significantly shortened the median waiting list time (274 vs 736 days, P<.001). Conclusions: We show safe use of CDCHR donor kidneys and good 1-year graft function. With continued use of these organs and careful follow-up care, we will be better able to gauge donor risk and match it to recipient need to expand the donor pool and optimize patient benefit. ©2011 American Medical Association. All rights reserved.