Introduction: Fecal bifidobacteria response after Bifidobacterium breve M-16 V supplementation was comparable in preterm small (SGA) versus appropriate for gestational age (AGA) infants. Objectives: To compare clinical outcomes between preterm SGA versus AGA infants after routine probiotic supplementation (RPS) with Bifidobacterium breve M-16V (3 × 109 CFU/day). Design: Retrospective cohort study (June 2012–August 2015) comparing outcomes between preterm (<34 weeks, subgroup: <29 weeks) SGA versus AGA infants after RPS with B. breve M-16 V using multivariable regression analysis. Primary outcome: necrotizing enterocolitis (NEC)≥Stage II/all-cause mortality. Secondary outcomes: NEC ≥ Stage II, all-cause mortality, late onset sepsis (LOS), postnatal age at full feeds (PAFF). Results: Outcomes in inborn 1380/1481 (162 SGA versus 1218 AGA) admissions were analyzed. Primary outcome “NEC ≥ Stage II /all-cause mortality” was higher in SGA versus AGA infants <29 weeks (21 versus 12%; p =.040), and showed trend toward reduction (8 versus 6%; p =.057) in AGA <34 weeks. NEC ≥ Stage II, LOS, and all-cause mortality was comparable in SGA versus AGA infants <34 weeks (3 versus 2, 9 versus 8, 9% versus 6%) and <29 weeks (5 versus 4, 16 versus 9, 18% versus 19%), respectively. Median (IQR) PAFF was significantly higher in SGA versus AGA infants <34 weeks (8 (6–12) versus 7 (5–10) days), and <29 weeks (14 (12–17) versus 11 (8–16) days). Conclusions: NEC, LOS and all-cause mortality rates were similar in preterm SGA versus AGA infants after RPS with Bifidobacterium breve M-16 V, but PAFF was higher in SGA infants.