<p><strong>OBJECTIVE: </strong>Determine impact of using delivery criteria to initiate antibiotics among very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. STUDY&nbsp;DESIGN: Single site cohort study from 01/01/2009 to 01/31/2020. After 04/2017, infants delivered by Cesarean section, without labor or membrane rupture were categorized as low-risk for early-onset infection and managed without empiric antibiotics. We determined effect of this guideline by pre-post, and interrupted time-series analyses.</p>

<p><strong>RESULTS: </strong>After 04/2017, antibiotic initiation ≤3 days decreased among low-risk VLBW (62% vs. 13%, p &lt; 0.001) and low-risk ELBW (88% vs. 21%, p &lt; 0.001) infants. In time series analysis, guideline was associated with decreased initiation among low-risk ELBW infants. In contrast, low-risk VLBW infants demonstrated decreased antibiotic initiation throughout study period. Incidence of confirmed infection, death, or transfer ≤7 days age was unchanged.</p>

<p><strong>CONCLUSION: </strong>Delivery criteria may be used to optimize early antibiotic initiation among preterm infants without short-term increase in adverse outcomes.</p>