cytomegalovirus (CMV) is the most important viral pathogen after organ transplantation. The risk of developing a CMV disease in transplanted patients depends on a combination of host and viral factors. For example, it is well established that the serological CMV status of the donor and recipient is a very important risk factor for developing a CMV disease, especially in the negative donor/recipient sub-group (D +/R-). On the other hand, it is not completely elucidated if specific viral polymorphisms may influence the evolution in the therapeutic response in patients with CMV infection. We assessed the role of the different genotypes of CMV glycoprotein (gB) on the clinical and virological development of CMV disease in patients transplanted with organs under antiviral treatment, and in doing so, we studied 239 patients transplanted from organs included in a multicentric study evaluating two antiviral medicines used to treat CMV disease. The genotyping of CMV gB was performed using quantitative real-time PCR at the start of antiviral treatment. CMV gB polymorphisms allow discrimination against four distinct genotypes (GBL, GB2, GB3 and GB4). We defined a mixed infection as the simultaneous presence of more than one genotype in a patient with CMV disease. The prevalence of different gB genotypes was 26 % for GBL, 10 % for GB2, 10 % for GB3, and 5 % for GB4, while mixed infections were present in 49 % of cases. D +/R + patients had more frequent mixed infection than D +/R- patients (40 % vs 12 %, -< 0.001). Patients with mixed infection had a higher median of the CMV viral load and a longer viral eradication time compared to patients with a single genotype infection (p = 0.005 and p = 0.026, respectively). In a multivariate model, mixed infections were an important predictor of the failure of virus eradication on day 21 when antiviral treatment started (rib ratio between mixed infection vs. single genotype infection = 2.66, 95 % confidence interval = 1.31 to 5.38, p = 0.007). No effect of the gB genotype on the development of clinical or virological recidivism of CMV infection has been observed. However, mixed infections with several gB genotypes are associated with a higher viral load and a delay in viral eradication following antiviral treatment.