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To determine whether 24% sucrose solution given orally before insertion of a peripheral intravenous (PIV) catheter decreases neonatal pain.Prior studies of pain caused by heel and arterial needlesticks found oral administration of 24% sucrose to significantly blunt pain during these painful procedures. No studies have evaluated this treatment with needlestick pain associated with PIV catheter insertion.Oral 24% sucrose or placebo solution was administered 2 minutes prior to PIV catheter insertion. Outcome measures were obtained prior to, during, and for 5 minutes after PIV catheter insertion. Investigators and caregivers were blinded to group assignment. Data were analyzed with longitudinal analysis of repeated measures, with P < .05 for significance.A total of 40 neonates (24% sucrose: N = 20; placebo: N = 20) were studied. Pain scores significantly increased from 3.2 ± 1.6 to a maximum of 7.6 ± 3.8 at the time of catheter insertion, returning to baseline levels 8 minutes after PIV catheter insertion (P < .001). No significant differences were found in pain, heart rate, or noninvasive oxygen saturation (SpO2) between the sucrose and placebo groups (P > 0.05).Results from this study did not find that 24% sucrose administered prior to PIV catheter insertion altered the infant's pain response.Since this is the first study to evaluate the pain-blunting effects of 24% sucrose administration before PIV catheter insertion, replication of this study is needed before widespread application of findings.