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Objective This study investigated the associations between caregiver verbal reassurance and infant pain-related distress during immunization over the first year of life. The relationships between verbal reassurance and caregiver emotional availability (EA) were also examined. Finally, EA was investigated as a moderator of the relationship between verbal reassurance and infant pain. Methods A cross-sectional analysis was conducted with 606 infants (and their parents) at 4 different ages (n = 376 at 2 months, n = 455 at 4 months, n = 484 at 6 months, and n = 407 at 12 months). Results Verbal reassurance was positively associated with infant distress across all four ages. EA was only negatively related to verbal reassurance at 12 months of age. EA was not a significant moderator at any age. Conclusion Findings demonstrate consistent but small relationships between verbal reassurance and infant pain over the first year of life.