BACKGROUND: Acute upper respiratory tract infections (URTIs) contribute substantially to pediatric morbidity and mortality worldwide. Prevention of these infections in childhood is a very important public health challenge. Previous systematic reviews, including both adult and childhood populations, have reported that probiotics seem promising, but with modest evidence. This study aimed to focus on prophylactic probiotic use in the prevention of URTIs in childhood. METHODS: Relevant trials on two databases were identified in a systematic review, from inception to June 2014. Study selection, data extraction and quality assessment were carried out by two reviewers. In this review, the effects of probiotics, particularly the Lactobacillus and Bifidobacterium strains, on the incidence and symptom scores of URTI in otherwise healthy children were evaluated for the first time. This review comprises 14 randomized controlled trials (RCTs) applied to a pediatric population with high-quality methodology. RESULTS: This systematic review suggests that probiotics in immunocompetent children have a modest effect both in diminishing the incidence of URTIs and the severity of the infection symptoms. CONCLUSIONS: At least one beneficial effect of prophylactic probiotic was observed in the majority of RCTs. Even a minimal reduction of 5 - 10% in the incidence of URTIs would have an important clinical and economic mpact on societies. Furthermore, the long-term administration of probiotics appeared to have a good safety profile in childhood and none of the studies reported any serious adverse events related to the probiotic strain.