The objective of this study was to assess the efficacy and safety of oral 30% dextrose during venepuncture in neonates. Neonates admitted in the Special Care Nursery for jaundice from September 200 to January 2001 were recruited for this double-blind randomised controlled trial. The intervention consisted of administration of either 2 ml of oral 30% dextrose or 2 ml of sterile water 2 minutes before venepuncture. The primary outcome measure was the cumulative Neonatal Infant Pain Scale (NIPS) score at 3 minutes after venepuncture and the duration of cry assessed from a videotaped recording. Twenty-six neonates received 30% dextrose and 26 neonates received sterile water. The cumulative NIPS score at 3 minutes (median, IQR) after venepuncture for neonates given 30% dextrose (13, 6.8-21) was significantly (p = 0.03) lower than that for neonates given sterile water (21, 13.8-21). The duration of cry in neonates given 30% dextrose (median 45 sec IQR 1.5-180.8 sec) was significantly (p = 0.03) shorter than that in neonates given sterile water (median 191 sec IQR 52.3-250 sec). No neonates developed diarrhoea, fever or rash during the 24 hour observation period. Both the intra-rater (ICC 0.993 95% CI 0.988-0.996) and inter rater (ICC 0.988 95% CI 0.980-0.993) agreement on the 3-minute NIPS score were good. In conclusion oral 30% dextrose given 2 minutes before venepuncture was effective in reducing neonatal pain following venepuncture. It is a simple, safe and fast acting analgesic and should be considered for minor invasive procedure in term neonates.