BACKGROUND: Upper respiratory tract infections (URTIs) are common and burdensome infectious illness. Several trials have reported that probiotics can prevent URTIs in adults. OBJECTIVES: To evaluate the efficacy and safety of probiotics in the prevention of URTIs in adults. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were searched for reports published from database inception to May 14, 2020. Randomized controlled trials (RCTs) comparing probiotics with placebo for the prevention of URTIs in adults were included. RESULTS: Six RCTs with 1551 participants were included. Compared with the placebo group, the probiotics intervention group significantly reduced the incidence of URTI episodes (RR: 0.77; 95% CI: 0.68 to 0.87; P < 0.0001; I (2) = 26%), the episode rate of URTIs (rate ratio: 0.72; 95% CI: 0.60 to 0.86; P = 0.0002; I (2) = 99%), and the mean duration of one episode of URTI (MD: -2.66; 95% CI: -4.79 to -0.54; P = 0.01; I (2) = 80%). The adverse events of probiotics were mainly mild gastrointestinal symptoms. There were no significant differences in occurrence rate of adverse effects between probiotics intervention and placebo group (rate ratio: 1.01; 95% CI: 0.80 to 1.26; P = 0.96; I (2) = 99%). CONCLUSION: Low-quality evidence provides support that probiotics have potential efficacy for preventing URTI episodes in adults. More trials are required to confirm this conclusion.