We assessed the impact of antiviral preventive strategies on the incidence of herpes-simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV/VZV infection were assessed by Cox PH regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis [(val)ganciclovir (n=1126) or (val)acyclovir (n=138)]. Incidences for HSV and VZV infections were 28.9 and 12.1 cases per 1000 person-years, respectively. Incidence of HSV/VZV infections at 1-year post-transplant was 4.6% (95% CI 3.5-5.8) in patients receiving antiviral prophylaxis vs. 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was particularly observed for HSV infections: 3% (95% CI 2.2-4) vs. 9.8% (95% CI 8.4-11.4), respectively. A lower rate of HSV/VZV infections was also seen in donor or recipient CMV-positive patients receiving (val)ganciclovir prophylaxis as compared to a preemptive approach. Female gender (HR 1.663, p=0.001), HSV seropositivity (HR 5.198, p