As cytomegalovirus (CMV) infection frequently occurs in simultaneous pancreas kidney transplantation (SPKT), most centers use general ganciclovir prophylaxis. The aim of the study was to analyze the impact of CMV in a patient cohort with preemptive therapy only. Incidence, course and risk factors of CMV infection were retrospectively analyzed in 94 adult SPK recipients without prophylaxis. Patients with asymptomatic pp65-antigenemia were treated preemptively with intravenous ganciclovir for 14 days. Survival rates after 1, 3, and 5 years were 98%, 97%, and 94% for patients, 96%, 94%, and 88% for renal grafts and 88%, 85%, and 82% for pancreas grafts. CMV infections occurred in 51% of patients and CMV syndrome in 16%. No tissue-invasive disease was observed. Thirty-eight per cent of patients with CMV infection developed a recurrence. Risk factors for CMV in multivariate analysis were the D+/R- constellation, acute rejections, anti-rejection therapy and coronary heart disease. CMV had no impact on patient or graft survival, occurrence of acute or chronic rejection and bacterial infections. Preemptive therapy seems to be safe and effective in SPK recipients, but as the present study was retrospective, prospective randomized studies are needed to confirm our results.