Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection in the intensive care unit, resulting in a high burden of illness, mortality and increased cost. The literature around the cost-effectiveness of probiotics in prevention of health-care associated infections has not been previously well-described, and a definitive health economic evaluation alongside a well-designed randomized control trial assessing probiotic prophylaxis has not been previously performed. This thesis consists of 3 separate manuscripts (with 2 published in peer-reviewed journals and 1 pending). The theme of this thesis was to: (1) describe the literature about the cost-effectiveness of probiotics in hospitalized patients in preventing healthcare-associated infections; (2) design a protocol for an economic evaluation alongside a randomized control trial (RCT) examining probiotic prophylaxis of VAP; and then (3) perform and analyze the health economic evaluation presented in the protocol. The first component of this thesis is a systematic review of probiotic prophylaxis of healthcare-associated infections in hospitalized patients. We performed an extensive search including multiple databases which found 7 studies. Probiotics demonstrated favourable cost-effectiveness in 6 of 7 (86%) economic evaluations, with 3 studies being manufacturer-supported, all suggesting cost-effectiveness. Certainty of cost-effectiveness evidence was very low due to risk of bias, imprecision and inconsistency using the GRADE approach. Hence further RCTs with economic evaluations were stated as a solution. The second component of this thesis is a study protocol for an economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT), which assessed the efficacy of probiotic prophylaxis in the prevention of healthcare-associated infections (specifically VAP). The third component of this thesis is the cost-effectiveness analysis performed utilizing the individual patient data from PROSPECT to produce the economic evaluation (E-PROSPECT). As of the date of thesis submission, PROSPECT is still pending publication, and hence E-PROSPECT is also pending analysis and publication. However, I have prepared a draft manuscript (along with figures and tables) that will be produced at the conclusion of E-PROSPECT for thesis committee review. / Thesis / Master of Health Sciences (MSc) / Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection in the intensive care unit, resulting in a high burden of illness, mortality and increased cost. The literature around the cost-effectiveness of probiotics in prevention of health-care associated infections has not been previously well-described, and a definitive health economic evaluation alongside a well-designed randomized control trial assessing probiotic prophylaxis has not been previously performed. This thesis consists of 3 separate manuscripts (with 2 published in peer-reviewed journals and 1 pending). The theme of this thesis was to: (1) describe the literature about the cost-effectiveness of probiotics in hospitalized patients in preventing healthcare-associated infections; (2) design a protocol for an economic evaluation alongside a randomized control trial (RCT) examining probiotic prophylaxis of VAP; and then (3) perform and analyze the health economic evaluation presented in the protocol. The first component of this thesis is a systematic review of probiotic prophylaxis of healthcare-associated infections in hospitalized patients. We performed an extensive search including multiple databases which found 7 studies. Probiotics demonstrated favourable cost-effectiveness in 6 of 7 (86%) economic evaluations, with 3 studies being manufacturer-supported, all suggesting cost-effectiveness. Certainty of cost-effectiveness evidence was very low due to risk of bias, imprecision and inconsistency using the GRADE approach. Hence further RCTs with economic evaluations were stated as a solution. The second component of this thesis is a study protocol for an economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT), which assessed the efficacy of probiotic prophylaxis in the prevention of healthcare-associated infections (specifically VAP). The third component of this thesis is the cost-effectiveness analysis performed utilizing the individual patient data from PROSPECT to produce the economic evaluation (E-PROSPECT). As of the date of thesis submission, PROSPECT is still pending publication, and hence E-PROSPECT is also pending analysis and publication. However, I have prepared a draft manuscript (along with figures and tables) that will be produced at the conclusion of E-PROSPECT for thesis committee review.