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Immunization site pain is a common and unpleasant experience for both children and adults. It is a source of anxiety and distress and may ultimately result in nonadherence to vaccination schedules. There is limited information on how different brands of vaccines affect the intensity of immediate pain at the time of vaccine injection.Children in the United Kingdom (n = 178) were randomized to receive a booster dose of either the 10- or the 13-valent pneumococcal conjugate vaccine (PCV-10 or PCV-13). Immediate immunization site pain was assessed using validated pain assessment tools and crying time to investigate factors that may interfere with parental compliance to vaccination.Pain measurements were available for n ≥ 74 and n ≥ 78 PCV-10 and PCV-13 recipients, respectively. PCV-13 recipients had significantly higher scores on the observer-rated modified behavioral pain scale than did those receiving PCV-10. No significant differences in the induction of pain between the 2 vaccines were found when a parent-rated pain assessment tool or crying time was used.PCV-10 administration was associated with slightly less acute pain compared with the injection of PCV-13, but the size of the difference was small and is of unknown clinical significance.