the role that cytomegalovirus (CMV) plays in inflammatory bowel disease (IBD) is controversial. The diagnosis of CMV infection in IBD depends on viral identification with hematoxylin-eosin (HE) or immunohistochemistry (IHC). Our aim was to compare the sensitivity of HE and IHC for this diagnosis in IBD patients. a case-control study. Our database was searched for IBD patients with HE- or IHC-based CMV-positivity from 1997 to 2007. Controls were selected among IBD inpatients matched for age and year of diagnosis with CMV. Their clinical characteristics were analyzed. HE and IHC were performed on biopsies from cases and controls at 6 months before and after inclusion in the study. In the statistical analysis, p values below 0.05 were considered significant. ten IBD patients with CMV infection were identified. IBD-CMV patients were more steroid-resistant or steroid-dependent (p = 0.03), and underwent a higher number of colonic biopsies (p = 0.03). From 97 biopsies analyzed, 12 were HE-negative and IHC-positive, and 3 showed reversed results. The sensitivity of HE was 58.6%, 95% CI (38.9-78.3), and that of IHC was 89.7%, 95% CI (76.8-100). We did not find a good level of agreement between both techniques: kappa value 0.55, 95% CI (0.36-0.75). CMV positivity with IHC was associated with the use of more than one immunosuppressant drug, OR 13.5, 95%CI (1.2-152.2). Antiviral treatment was useful for CMV patients with steroid-dependent and steroid-refractory IBD. IHC shows a 30% higher sensitivity than HE for the diagnosis of CMV infection in IBD patients. There is no good level of agreement between both histological techniques.