To compare a short course of antibiotics (48 to 96 hours) and a standard course of antibiotics (7 days) for probable neonatal sepsis. Randomized, controlled, open-labeled trial with blocking and stratification according to birth weight. Tertiary care, referral, teaching hospital in Northern India. Neonates >30 wks gestation and >1000 g at birth, with probable sepsis (clinical signs of sepsis, raised C reactive protein) were enrolled. Babies with major malformations, severe birth asphyxia, meningitis, bone or joint or deep-seated infection, those who were already on antibiotics, and those undergoing surgery were excluded. Neonates, who had clinically remitted on antibiotic therapy by the time a sterile blood culture report was received were randomized. In the intervention arm, antibiotics were stopped after the 48 hour culture was reported sterile. In the control arm, antibiotics were continued to a total of 7 days. Treatment failure defined as reappearance of signs suggestive of sepsis within 15 days of stopping antibiotics, supported by laboratory evidence and adjudicated by a blinded expert committee. 52 neonates were randomized to receive a short course or 7 day course (n=26 each). Baseline variables were balanced in the 2 groups. There was no significant difference in the treatment failures between the 2 groups (3 babies in the 7-day group vs none in short course group, P=0.23). No difference in the treatment failure rates could be identified between short course and 7-day groups among neonates >30 weeks and > 1000 grams with probable sepsis.