Background: Probiotics are protective against Clostridioides difficile infection and antibiotic-associated diarrhea, and they may decrease risk of infections following complex abdominal surgeries. Infectious risks associated with probiotic use are not well described in the literature. We describe probiotic use among patients with bloodstream infections (BSIs) due to organisms typically found in probiotics. Methods: Patients with positive blood cultures with Lactobacillus spp, Saccharomyces spp, and Bifidobacterium spp at our large academic hospital from October 2016 through October 2019 were identified using Theradoc, a clinical surveillance tool. Clinical data and orders for probiotics, including probiotic capsules, probiotic yogurt, and kefir, were extracted from the electronic medical record. Cases were considered distinct if the cultures were collected 7 or more days apart. True infections were defined as positive cultures which were treated with antimicrobials and had provider documentation outlining clinical relevance of culture data. Results: Among 26 distinct episodes of BSI, 16 (62%) were considered true infections. The remaining 10 cases were interpreted as contaminants or of unclear significance. Of the 16 cases representing true infection in 14 patients, 6 (38%) had received probiotics in the hospital in the preceding month. Among these patients, 5 had Lactobacillus bacteremia and had received Lactobacillus capsules, probiotic yogurt, and/or kefir. One patient had Saccharomyces fungemia following receipt of probiotic yogurt and kefir. All 6 patients with BSI possibly related to probiotic use had an antecedent gastrointestinal procedure or surgery within a month of the BSI, and 2 had intra-abdominal abscesses from which the same organism was cultured. Of the 16 true BSIs, 9 occurred in immunocompromised hosts, but antecedent probiotic use was confirmed in only 1 of these cases. Two episodes caused by different organisms occurred within the same month; all other episodes were >60 days apart. Conclusions: In our retrospective review of BSIs with organisms typically found in probiotics over a 3-year period at a large academic hospital, more than one-third of those with clinically relevant BSIs had antecedent probiotic use within the hospital. All patients with infections possibly related to probiotic use had recent gastrointestinal procedures or surgery, raising concern for probiotic use following interventions that increase the risk for gastrointestinal tract leakage or translocation. Further research is necessary to assess the risk of bloodstream infection in postoperative patients treated with probiotics.