Anti-tumor necrosis factor (anti-TNF) is an effective biological agent for the treatment of moderate-to-severe active ulcerative colitis (UC) refractory to conventional therapy. On the other hand, anti-TNF therapy is strongly associated with a potential risk of tuberculosis (TB). Active TB is a critical complication that makes it difficult to treat patients who require anti-TNF for the treatment of UC refractory to conventional therapy. Based on the clinical guidelines, patients with inflammatory bowel disease (IBD) are strongly recommended to screen for latent TB before anti-TNF administration. Considering the possibility of active or reactivated TB related to anti-TNF therapy, all patients with IBD should be monitored closely for TB during anti-TNF therapy, irrespective of the screening results for latent TB. In particular, the risk of anti-TNF-related multidrug-resistant TB (MDR-TB) in patients with IBD has not been elucidated. This paper reports the first case of disseminated MDR-TB that developed in a UC patient receiving infliximab despite the negative evaluation for latent TB screening.