Summary Background Preliminary data have suggested that interleukin‐2 receptor blockade with basiliximab may increase steroid sensitivity. We have previously reported a small case series demonstrating the potential of basiliximab as a novel agent for the treatment of steroid‐resistant ulcerative colitis. Aim To report further experience of the efficacy and safety of treatment with the interleukin‐2 receptor blocking monoclonal antibody basiliximab, in addition to steroids, for the treatment of severe and moderate steroid‐resistant ulcerative colitis. Methods Twenty patients were enrolled – 13 patients with moderate steroid‐resistant ulcerative colitis (Ulcerative Colitis Symptom Score: ≥6) and seven patients with severe steroid‐resistant ulcerative colitis. All were given a single dose of 40 mg basiliximab plus standard steroid therapy in an open‐label, uncontrolled trial. Primary end point was clinical remission within 8 weeks (Ulcerative Colitis Symptom Score: ≤2). Results Within 8 weeks, 10 of 20 (50%) patients achieved clinical remission (seven of 13 moderate, and three of seven severe). At 24 weeks, 13 of 20 (65%) patients were in clinical remission. Five patients required colectomy (four severe, one moderate ulcerative colitis) and one required rescue ciclosporin (moderate ulcerative colitis). Two patients developed herpes zoster, but treatment was generally well tolerated. Conclusions Basiliximab appears to promote prolonged remission after a single treatment. Taken in combination with previously reported data, basiliximab shows particular promise in moderate steroid‐resistant ulcerative colitis.