BACKGROUND: Efficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results. AIM: To assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy. METHODS: Pubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects. RESULTS: Eight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p