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Introduction: There is accumulating evidence supporting the use of probiotics, which are defined as “live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host”, as a preventive measure against respiratory tract infections (RTI). Two recent meta-analyses showed probiotic consumption (daily intake of 107 to 1010 CFU in any form for up to 3 months) significantly reduced RTI duration, frequency, antibiotic use and work absenteeism. Objectives: The aim of this study was to assess the impact of probiotic use in terms of number of RTI episodes and days averted, and the number of antibiotic prescriptions and missed workdays averted, in the general population of Canada. In addition, the corresponding economic impact from both a healthcare payer and a productivity perspective was estimated. Methods: A microsimulation model was developed to reproduce the Canadian population (sample rate of 1/1000 = 35 540 individuals) employing age and gender. RTI incidence was taken from FluWatch consultation rates for influenza-like illness (2013–14) and StatCan all-cause consultations statistics. The model was calibrated on a 2.1% RTI annual incidence in the general population (5.2 million RTI days) and included known risk factors (smoking status, shared living conditions and vaccination status). RTI-related antibiotic prescriptions and work absenteeism were obtained from the literature. Results: The results indicate that probiotic use saved 573 000–2.3 million RTI-days, according to the YHEC–Cochrane scenarios respectively. These reductions were associated with an avoidance of 52 000–84 000 antibiotic courses and 330 000–500 000 sick-leave days. A projection of corresponding costs reductions amounted to Can$1.3–8.9 million from the healthcare payer perspective and Can$61.2–99.7 million when adding productivity losses. Conclusion: The analysis shows that the potential of probiotics to reduce RTI-related events may have a substantial clinical and economic impact in Canada. [ABSTRACT FROM AUTHOR]