The safety and efficacy of probiotics during severe illness has been a subject of ongoing interest. The impact of probiotics can worsen nutritional status, which could potentially result in a deterioration of the patient's overall life-threatening status. This systematic review and meta-analysis evaluated the safety and efficacy of probiotics in reducing intensive care unit (ICU)-acquired infections in adult critically ill patients. PubMed and Cochrane library databases for the period 2011-2020 were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) methodology was used to search for randomized controlled trials that evaluated the use of probiotics among critically ill patients. No significant difference was observed between probiotics and control groups in terms of the mortality rate (risk ratio 1.13, 95% confidence interval .82 to 1.55, P = .46). Probiotics, however, provided a significant reduction in ICU-acquired infections (risk ratio .73, 95% confidence interval .58 to .93, P = .01). The use of probiotics seems to play a role in decreasing the incidence of ICU-acquired infections. Also, a potential reduction in terms of the incidence of diarrhea has been reported, with no examples of adverse incidents, suggesting probiotics are safe.