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Background: Cytomegalovirus (CMV) is a major pathogen affecting solid organ transplant (SOT) recipients. Prophylactic strategies have decreased the rate of CMV infection/disease among SOT. However, data on the effect of current prophylactic strategies for simultaneous pancreas-kidney (SPK) or pancreas after kidney (PAK) transplant remain limited. We report our experience of CMV prophylaxis in SPK/PAK recipients., Methods: A total of 130 post-SPK/PAK patients were analyzed retrospectively for the rate of CMV and the risk factors associated with the acquisition of CMV. All patients received antiviral prophylaxis. The follow-up period was one yr post-transplant or until death., Results: The rate of CMV post-SPK/PAK transplant was 24%, 44%, and 8.2% among the whole cohort, the D+/R- and the R+ groups, respectively. Median time of prophylaxis was 49 (0-254) d. In the whole cohort, risk factors for CMV infection/diseases were D+/R- CMV status (odds ratio [OR] = 16.075), preceding non-CMV (infection caused by bacteria or fungi and other viruses) infection (OR = 6.362) and the duration of prophylaxis (OR = 0.984). Among the CMV D+/R- group, non-CMV infection was the only risk factor for CMV disease (OR = 10.7)., Conclusions: Forty-four per cent (25/57) of the D+/R- recipients developed CMV infection/disease despite CMV prophylaxis. Current CMV prophylaxis failed to prevent CMV infection/disease in this group of patients., (© 2013 John Wiley & Sons A/S.)