Objective To investigate the efficacy, safety and side effects of Saccharomyces boulardii (S. boulardii) in the prevention and treatment of antibiotic-associated diarrhea (AAD) in elderly patients with lower respiratory tract infections. Methods A total of 127 hospitalized older patients with lower respiratory tract infections admitted in our department from March 2016 to May 2017 were prospectively enrolled in this study, and they were randomly divided into intervention group (n=63, antibiotics+preventive oral administration of S. boulardii powder) and control group (n=64, antibiotics+same volume of placebo). The incidence rate of AAD, other abdominal symptoms, fecal coccus-bacillus ratio and drug side effects were compared between the 2 groups. SPSS statistics 19.0 was used to perform the statistical analysis. Student′s t test, Chi-square test or Fisher exact test was employed for comparison between groups based on different data types. Results The incidence rate of AAD was 11.11%(7/63) and 26.56%(17/64) respectively in the intervention group and the control group. The daily stool frequency was (2.69±1.24) and (4.27±1.65) times, and the percentage of the subjects with watery stool were 1.59%(1/63) and 18.75%(12/64), all with significant differences between the 2 groups (P<0.05). There were less patients with fecal coccus-bacillus ratio >1/2 in the intervention group than the control group [3.17%(2/63) vs 18.75%(12/64), P<0.05]. No severe adverse reaction related to S. boulardii occurred in the intervention group. Conclusion Preventive administration of S. boulardii can reduce the incidence of ADD, lead to no more obvious side effects compared with routine therapy, and doesn′t cause severe adverse reaction relative to the bacteria in the elderly with lower respiratory infection.