Abstract Background The presence of CMV in blood is quite common in patients with severe flares of ulcerative colitis (UC) and Crohn’s disease (CD) and seems to predict an adverse outcome. The impact of antiviral treatment on CMV in this setting (indications and drug options) is an unresolved issue. Our aim was to reassess the CMV role in patients with IBD hospitalised for severe exacerbations, analysing the relationship between CMV positivity, clinical characteristics, antiviral therapy and disease outcomes. Methods We evaluated a homogeneous cohort of 97 consecutive patients with IBD hospitalised from 2012 to 2018. Data regarding age, gender, smoke, familial predisposition, type of IBD, extent, according to Montreal classification, disease activity (clinical and endoscopic), therapy at the time of relapse were registered in a dedicated database. CMV was tested by PCR in whole blood. The relationship between antiviral therapy and disease outcomes (rate of colectomy, mortality) was analysed. Results Among the 97 patients, 51 were females. In the UC group (67 patients, 69.1%), mean age was 48,8, SD ± 17,7 whereas in the CD group (30 patients, 31%), mean age was 39,9 years (SD ± 15,2). Fifteen per cent of patients had a family predisposition for IBD. There were no differences at baseline between UC and CD, except disease duration (longer in UC) and therapy at the time of relapse (high dose steroids more common in UC). Thirty-one patients (32 %) tested positive for CMV on PCR. Smoking habit, shorter disease duration, therapy on admission (high dose steroid and/or immunomodulators) and endoscopic activity assessed by Mayo endoscopic sub-score were the variables significantly related to CMV positivity. Antiviral therapy was adopted in 22% of patients and the decision to treat was based on clinical judgement and viral load. Treated patients had higher endoscopic activity than untreated (Mayo sub-score 3 vs. 2,6, p < 0,004). The mean hospital duration was longer in treated patients 22.3 ( ± 11.1) days, vs. 14,8(+/−8,6) days. 3 patients underwent surgery within 90 days, 2 patients died; all of them were positive for CMV DNA. No significant differences were observed on either colectomy or mortality rate in relation to the use of antiviral therapy. Conclusion This single-centre study confirms that the CMV reactivation during disease flares of IBD is common and related to disease duration, severe endoscopic lesions, and immunosuppression (high dose steroids and/or immunomodulators).Antiviral drugs do not seem to modify surgical outcomes or mortality but increase the hospitalisation length. However, the retrospective design and the limited sample size of the study do not allow to draw definitive conclusions: the real impact on outcome and the role of antiviral therapy will require adequately powered prospective studies.