Background and Aims: Cytomegalovirus CMV infection often reactivates in the course of inflammatory bowel disease, but the significance of this remains disputable. Our aim was to evaluate whether severity of CMV colitis is associated with colectomy risk in ulcerative colitis UC patients. The secondary aim was to evaluate agreement between immunohistochemistry IHC and blood CMV polymerase chain reaction PCR. Methods: UC patients with CMV assessment of the colon, hospitalised in a referral unit between 2005 and 2012 were retrospectively identified. The course and severity of the disease were analysed, with inflammation graded histologically across the range 0–3. The numbers of CMV IHC-positive cells per biopsy section were counted, and results for blood CMV PCR were also retrieved. Data on colectomies were also collected. Results: Of 141 patients, 95 were analysed, with 33 found to be CMV IHC-positive and 62 negative. The colectomy risk was significantly higher in patients with ≥ 5 IHC-positive cells, as opposed to those with none or less than 5 p = 0.014 with median follow-up of 1.9 and 3.2 years, respectively. The CMV IHC-positive patients had lower haemoglobin median 11.0g/dl vs 12.0; p = 0.028 and albumin median 29.5g/l vs 33.1; p = 0.038 levels and more intense histological inflammation p = 0.020 compared with CMV IHC-negative patients. There was substantial agreement between IHC and blood PCR Cohen’s kappa coefficient 0.72. Conclusions: Five or more CMV IHC-positive cells per biopsy section were indicative of a greater colectomy risk. CMV infection was related to more severe inflammation. Blood CMV PCR is a useful tool in UC.