Human herpesvirus 6 (HHV-6) infection is potentially life-threatening to immunosuppressed patients. There is a lack of information regarding the risk and the clinical manifestations of primary HHV-6 infection in solid-organ transplant recipients. We prospectively evaluated patients undergoing solid organ transplantation with negative immunoglobulin (Ig) G antibodies against HHV-6 by means of HHV-6 quantitative polymerase chain reaction. Among 193 recipients, seven were HHV-6 seronegative (prevalence 3.6%). We detected a positive HHV-6 viral load in only one patient, and four patients seroconverted after one year posttransplantation. The patient with a positive HHV-6 viral load developed cholestatic hepatitis without fever and did not experience severe end-organ disease. In conclusion, our findings show a low incidence of symptomatic primary HHV-6 infection among seronegative solid-organ transplant recipients.