BACKGROUND AND AIMS: The role of probiotics in the treatment of diverticulitis is still not known. The aim of our study was to investigate whether balsalazide and/or VSL#3 is effective in preventing diverticulitis recurrence. MATERIALS AND METHODS: In this pilot study, 30 consecutive patients (19 males, 11 females, mean age 60.1 years, range 47-75 years) affected by uncomplicated diverticulitis of the colon were monitored. After obtaining remission, the patients were randomly assigned to one of the following groups as follows: group A, balsalazide 2.25 g daily for 10 days every month plus VSL#3 450 billions/day for 15 days every month and group B, VSL#3 alone 450 billions/day for 15 days every month. Primary end-point was considered the maintaining of remission throughout a 12-month follow-up. Secondary end-points considered were (1) the assessment of the overall scores at the end of the follow-up and (2) the effects of the two different treatments with regards to every symptom assessed. RESULTS/FINDINGS: One group A patient was withdrawn from the study at the 6th month and one group B patient was lost at the 6th month of follow-up. One group A patient (6.66%) showed relapse of symptoms at the 10th month of follow-up. At the end of follow-up, 11 patients were completely symptom-free (73.33%), whilst 2 patients complained of only mild, recurrent symptoms (13%). Two group B patients (13.33%) showed relapse of the disease at the 5th and 8th month of follow-up, respectively. At the end of follow-up, 8 patients were completely symptom-free (60%), 2 patients complained of mild, recurrent symptoms (13.33%), 1 patient (6.66%) complained of mild but continuous symptoms. No side effects were recorded throughout the follow-up in both groups. INTERPRETATION/CONCLUSIONS: Combination probiotic/anti-inflammatory drug was found better than probiotic treatment in preventing relapse of uncomplicated diverticulitis of the colon, even if without statistical significance.