Purpose The clinical impact of organ transplantation is limited by a persistent organ shortage. Due to concern about the potential risk of disease transmission, there has been inter and intra center variability in the use of Center for Disease Control or Public Health Service (CDC/PHS) high risk organs for transplantation. We have reviewed our single-center experience utilizing CDC/PHS high risk hearts and lungs to examine the impact of aggressive use of these organs. Methods Select CDC/PHS high risk donor organs were considered when nucleic acid testing (NAT) was negative. Patients were tested for Hepatitis B and C and HIV preoperatively and serially thereafter per center guidelines. Results From January 1, 2011 to October 23, 2018, Massachusetts General Hospital Transplant Center transplanted 108 thoracic organs from CDC/PHS high risk donors. Among these, there were 70 donor hearts accounting for 39.1% of all heart transplants during this period. Within this group there was one unexpected HCV seroconversion, determined to be from recipient high risk behavior. Thirty-eight of these organs were single or double lungs comprising 20.4% of all lungs transplanted in this interval. Among the lung recipients, there has been 9 (23.6%) documented organ seroconversions of HBV core antibody (HBcAb) status negative to positive. Of these, each recipient was negative by NAT and for HBV surface antigen (HBsAg). Within the entire cohort, there have been no seroconversions from infected donors. Conclusion Our center experience suggests that that there is limited risk to using CDC/PHS high risk organs when the NAT is negative. These results support aggressive use of NAT negative high organs to limit recipient waiting time and risk.