We performed an observational study with very-low-birth weight infants (VLBWI) ≤33 weeks of gestation born in centers of the German Neonatal Network (GNN; (total n = 8534, n = 6229 received probiotics). The primary objectives of our study were (a) to assess the effect of Lactobacillus acidophilus/Bifidobacterium infantis probiotics on growth in VLBWI during primary stay in hospital and (b) to determine whether this effect is modified by antibiotic exposure. In linear regression models the administration of probiotics was independently associated with improved weight gain [g/d; effect size B = 0.62 (95% CI: 0.37-0.87), p < 0.001], and higher growth rates for body length [(mm/d; B = 0.06 (95% CI: 0.04-0.08), p < 0.001] and head circumference [mm/d; B = 0.03, 95% CI: 0.02-0.04, p < 0.001]. This effect was pronounced in infants with postnatal exposure to antibiotics; i.e. weight gain [g/d; B = 0.66 (95% CI: 0.32-1), p < 0.001], growth rate body length [(mm/d; B = 0.09 (95% CI: 0.06-0.12), p < 0.001] and head circumference [mm/d; B = 0.04, 95% CI: 0.02-0.06, p < 0.001]. In the small subgroup that was available for analysis at 5-year-follow-up (with probiotics: n = 120 vs. without probiotics: n = 54) we noted a sustained effect of probiotics in infants who received postnatal antibiotics. Probiotics may improve growth in antibiotic-treated infants which needs to be confirmed in randomized-controlled trials.