OBJECTIVES: The purpose of the current study was to evaluate the effectiveness of vapocoolant for preschoolers’ immunization injection pain relief. STUDY DESIGN: 57 4- to 6-year-old children were randomized to vapocoolant alone or typical care conditions. Pain was measured at baseline and at injection via self-report, caregiver-report, nurse-report, and an observational scale. RESULTS: Self-report suggested that children in the vapocoolant alone condition demonstrated stronger increases in pain from baseline to injection than typical care. All other measures showed significant increases in pain from baseline to injection, but none indicted treatment effects. CONCLUSIONS: Consistent with prior studies, vapocoolant might not be an effective pain-management intervention for children’s intramuscular injections.