A multicenter, parallel-group, randomized, double-blind, active-controlled clinical trial, involving 169 outpatients at 9 centers, was conducted to assess the efficacy of a fixed bacterium combination of Lactobacillus gasseri and Bifidobacterium longum in the therapy of acute diarrhea. In particular, this clinical trial was designed to prove equivalent therapeutic efficacy of a fixed bacterium combination versus an exhaustive investigated mono-bacterium medicinal product. All patients, free to carry on usual daily activities, received 1 capsule 3 times a day of either a fixed bacterium combination of Lactobacillus gasseri and Bifidobacterium longum or Enterococcus faecium mono-bacterium. All treatments were continued for a maximum of 6 days in line with the normal course of acute diarrhea. Primary efficacy criterion was the severity and duration of diarrhea assessed by the ensemble of stool frequency as change from baseline and stool consistency at trial Day 2, 3 and 4, and time in days until normal bowel function (recovery). The median duration of diarrhea was 2.70 days versus 2.67 days (fixed bacterium combination of Lactobacillus gasseri and Bifidobacterium longum versus mono-bacterium Enterococcus feacium). The total mean difference of duration of diarrhea was 0.072 days. This result can be considered equivalent. However, the proportion of patients with complete recovery tended to be higher in the fixed bacterium combination group (92.6% versus 87.1%) resulting in a number needed to treat (NNT) of 18.1. The fixed bacterium combination reduced the number of unformed stools by 80% and the mono-bacterium by 75% during the first 2 days of treatment. Both treatments were well tolerated. Oral therapy with a fixed combination of Lactobacillus gasseri and Bifidobacterium longum shortens the duration and decreases the severity of acute self-limiting diarrhea in adults comparable to an effective mono-bacterium medicinal product. It therefore appears to be a useful and safe treatment for this disease.