Background: Probiotic treatment may be effective in diseases involving gut microflora and intestinal inflammation. In collagenous colitis (CC), a potential pathogenic role of the gut microflora has been proposed. The effect of probiotic treatment in CC is unknown. Our aim was to investigate the clinical effect of treatment with Lactobacillus acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 (AB-Cap-10) in patients with CC. Materials and Methods: Patients with CC and diarrhea were in a double-blind placebo-controlled study randomized (2:1) to AB-Cap-10 or placebo for 12 weeks. The primary end point was reduction in bowel frequency per week of ≥50%. Secondary end points were changes in bowel frequencies, stool consistency, stool weight, histopathology, and abdominal bloating and pain. Results: Twenty-nine patients were randomized: 21 to probiotics and 8 to placebo. Reduction in bowel frequency per week of ≥50% occurred in 6 of 21 (29%) and in 1 of 8 (13%) patients receiving probiotic and placebo, respectively (P = 0.635). No differences between treatments were observed regarding the secondary end points. Post hoc analysis showed a median reduction in bowel frequency per week from 32 (range 18–84) to 23 (range 11–56; P < 0.005), a reduction in number of days with liquid stools per week from 6 days (range 0–7 days) to 1 day (range 0–7 days; P < 0.005), and an increase in number of days with solid stools per week (P < 0.05) in the AB-Cap-10 group. Conclusions: AB-Cap-10 had no significant effect on the chosen end points. Post hoc analysis demonstrated amelioration of clinical symptoms in the AB-Cap-10 group, indicating that probiotic treatment may potentially influence the disease course of CC.