PurposeFactors influencing infants' behavioral and vocal (cry) response to painful stimuli are explored to improve pain management plans for infants undergoing immunizations. Design and MethodsAn observational study design was used. Pain responses of 60 to 75 days-old infants (44% male vs 56% female) undergoing two-month immunization injections were videotaped and coded using the Modified Behavioral Pain Scale (MBPS), and duration of total crying time during injection was recorded. The influences of five factors (gender, caregiver attendance, previous experience of nociception (circumcision), mode of delivery), and weight (birth and current) were examined at baseline, during and post-immunization. ResultsHigher birth weight was the most significant factor that reduced pain responses during (p = 0.001) and post-immunization (p = 0.03). A higher birth weight reduced full lung crying (p = 0.04), which reflects crying during injection as compared to total crying time. Vaginal delivery had a significant effect on behavioral pain responses of infants only post-immunization (p = 0.006). Parent's presence in the immunization room significantly reduced total crying time (p = 0.03). Uncircumcised male infants had a significant reduction in behavioral pain responses during immunization (p = 0.01) compared to circumcised infants. ConclusionsThe literature well supports the acknowledgement of early pain experience and its psychological consequences. Knowing and controlling for each of mentioned factors early in life during every painful procedure could improve coping mechanisms of infants for any painful procedures later in life. Practice ImplicationsControl of certain factors during early life experiences can modify pain of immunization.