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Introduction: Lactobacillus rhamnosus is an anaerobic or facultative anaerobic Gram-positive rod that is commonly found in the human gastrointestinal tract and vaginal tract. Infections secondary to L. rhamnosus have not been well illustrated in the literature. The purpose of this study was to describe the clinical courses of patients with L. rhamnosus infection in our institution. Materials and Methods: A retrospective chart review was performed on patients with the growth of L. rhamnosus or L. rhamnosus/casei from January 1, 2013, to December 31, 2017. Results: Forty-seven patients had growth of L. rhamnosus or L. rhamnosus/casei. Of these, 35 patients were included in the study who received therapy. Twenty patients (57.1%) presented with leukocytosis, 17 (48.5%) with fever, and 15 (42.8%) with abdominal pain. Twenty-three (66.1%) had intra-abdominal infection, 8 (22.3%) were bacteremic, and 4 (11.4%) had mediastinitis. Thirty-three patients (94.3%) had a polymicrobial infection. Eighteen (51.4%) patients had disruption of the gastrointestinal tract, 14 (40.0%) had underlying malignancy, and 11 (31.4%) had prior antibiotic exposure. Twenty (57.1%) patients clinically improved after therapy. However, the overall mortality rate was 56.2%, all of whom died of unrelated causes. Conclusion: Lactobacilli are organisms thought to have low pathogenicity. Our study identified cases of L. rhamnosus infections in a population of patients with serious underlying medical conditions.