BACKGROUND: Diverticular disease (DD) and irritable bowel syndrome (IBS) share a similar symptom pattern. However, comparative studies are flawed by different age at onset of symptoms. We aimed to verify whether clinical features distinguish DD from IBS. MATERIALS AND METHODS: Patients with DD or IBS, matched for age and gender (1/1) were consecutively recruited. Data on demographic parameters, voluptuary habits, inheritance of disease and symptoms were collected. Moreover, the association between pain > 24 h, and clinical parameters were evaluated. RESULTS: Ninety patients with DD and 90 patients with IBS (DD: F/M: 46/44; age: 50.9 years; IBS: 46/44; 50.4) were selected from an overall population of 1275 patients. Only nine patients with DD (10%) fulfilled the criteria for IBS diagnosis. Abdominal pain > 24 h was more prevalent in SDD than in patients with IBS (20 vs. 6 patients; P < 0·01). Furthermore, compared with IBS, patients with DD showed more episodes of pain > 24 h requiring medical attention (80% vs. 33%; P < 0·01). CONCLUSIONS: Abdominal pain lasting for more than 24 h discriminates patients with DD compared with those with IBS. Identifying this symptom could be an appropriate strategy to define the diagnosis and management.