Background: The use of probiotics as prophylaxis for necrotizing enterocolitis (NEC) in preterm infants is being increasingly practised. Objective: We report, for the first time, a case series of 3 preterm, very-low-birth-weight (VLBW) infants who developed bacteremia with Bifidobacterium longum on probiotic therapy with Infloran® containing viable B. longum. Methods: We retrospectively reviewed data of 3 infants (of gestational age <30 weeks and birth weight <1,230 g). They were admitted to the neonatal intensive care unit. Clinical data were retrieved from their medical records. Results: In infants 1 and 2, B. longum was isolated from the blood cultures when they were on probiotic therapy with Infloran or shortly after, respectively, and was interpreted as transient bacteremia. The clinical presentation of these infants did not require antibiotic treatment after the isolation of B. longum. Infant 3 developed an NEC despite probiotic therapy with Infloran and the blood cultures showed B. longum growth. This infant required explorative laparotomy and antibiotic treatment. The clinical isolates of B. longum and the strain of the Infloran capsule showed an identical profile on biochemical, mass-spectrometric and molecular analyses, suggesting a direct correlation between the administration of probiotics and bacteremia with B. longum in all 3 infants. Conclusions: The occurrence of bacteremia with bifidobacteria after its prophylactic administration in VLBW infants and its possible clinical consequences are a matter of concern. In the interests of safety, the use of probiotics in such a population should be indicated with caution and requires further investigation.