BACKGROUND: Distal ulcerative colitis (UC) is responsible for distressing symptoms and reduces quality of life (QoL). Oral and topical formulations of 5-amino-salicylic acid are the first line therapy for mild to moderate distal UC. OBJECTIVE: Our aim was to evaluate the impact of mesalazine treatment for mild to moderate ulcerative proctitis and proctosigmoiditis on patient QoL. METHODS: Ninety-three patients with mild to moderate ulcerative proctitis and proctosigmoiditis, initiating a treatment with Pentasa, were prospectively included. The primary endpoint was the change from baseline to W8 in patient health-related QoL (HRQoL) as measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) total score. RESULTS: More than 80% of patients were prescribed with a rectal formulation, either alone (47.9%) or with an oral formulation (35.1%), and 17.0% of patients were prescribed oral formulation alone. Mean SIBDQ score was improved at W8 in patients affected with mild and moderate disease ( P < 0.001 versus baseline in both groups, as well as in patients who achieved clinical remission ( P < 0.001). Patients who achieved clinical remission at W8 reached a mean change of +6.7 (+/-7.1), whereas those who did not achieve clinical remission had a mean change of +1.1 (+/-8.9). Seventy-five per cent of patients had an improvement of their disability index at W8. Fecal incontinence was also improved at W8. CONCLUSION: HRQoL measuring with the SIBDQ is proportionally related to disease activity in patients with distal UC treated with mesalazine.