Ulcerative colitis (UC) is a chronic inflammation of the large bowel characterized by diarrhea and a negative stool culture. However, several enteropathogens have been implicated as causative agents in UC. The differentiation between chronic infectious colitis (IC) and UC with concurrent infection is difficult owing to their similar clinical presentations. The study aimed to explore the presentations and diagnostic clues that enable differentiation between UC with concomitant infections and chronic IC. The study included 17 UC patients with a bacterial infection and 46 with chronic IC. The UC patients (47 ± 19 years) were younger than the chronic IC patients (58 ± 20 years) (P = 0.022). Bloody diarrhea was more common in UC than in chronic IC (58.8% vs 10.9%, P < 0.001). Previous antibiotic usage was a risk factor for chronic IC (5.9% vs 32.6%, P = 0.031). Malignancy was a common comorbidity of chronic IC (5.9% vs 34.8%, P = 0.022). UC patients had lower antibiotic response rates than chronic IC patients (60.0% vs 87.2%, P = 0.026). Aeromonas species and Clostridium difficile were common in both groups. Histological features of cryptitis and crypt abscess were useful in the diagnosis of UC (P = 0.052 and P = 0.016, respectively). Bloody diarrhea in a young adult, decreased response to antibiotic treatment, and results of endoscopy with biopsy are important features in the diagnosis of UC with bacterial infection.