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We examined responses of preterm infants to swaddling after a heel lance. Fifteen preterm infants from two postconceptional age (PCA) groups (Group 1: n = 7, PCA < 31 wk; Group 2: n = 8, PCA ≥ 31 wk) were observed for 30 minutes during blood sampling followed by routine care; blood sampling followed by swaddling; and no blood sampling and routine care. In both groups, blood sampling resulted in concurrent increases in heart rate and state of arousal, in negative facial displays, and in reductions in blood oxygen-saturation. After the blood was drawn, infants less than 31 weeks PCA exhibited an immediate and spontaneous return to behavioral patterns similar to those observed during the no-blood-sample condition, regardless of treatment condition. Infants 31 weeks PCA or older exhibited protracted behavioral disturbance that was significantly reduced by the use of swaddling. We discuss the significance of these findings.