Mesalamine with MMX Multi Matrix System® technology (hereafter referred to as MMX mesalamine) is an oral, high-strength (1.2 g/tablet), once-daily formulation of 5-aminosalicylic acid used for the treatment of ulcerative colitis. This new formulation has been designed to provide delayed and prolonged 5-aminosalicylic acid release throughout the colon. In recent clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g) effectively induced clinical remission and mucosal healing versus placebo in patients with active, mild-to-moderate ulcerative colitis. Once remission was achieved, MMX mesalamine effectively maintained disease remission in the majority of patients for at least 12 months. In this paper, we comprehensively review the results of studies exploring the clinical pharmacology, efficacy and safety of MMX mesalamine in patients with ulcerative colitis, and examine the implications of these findings on clinical practice.