The American Academy of Pediatrics recommendation that immunization of preterm infants with diphtheria-tetanus-pertussis (DTP) vaccine should begin at 2 months after birth, regardless of gestational age, is based on limited data. A prospective study was conducted to determine the immunogenicity and safety of DTP vaccine in preterm infants. One hundred ten preterm and 146 full term infants received doses of DTP at 2, 4 and 6 months after birth. Adjusted analysis of the antibody responses indicated that after three doses mean titers among preterm infants to each vaccine component were comparable to those of full term infants. Adjusted analysis of the incidence of adverse events indicated that the risk of adverse events in preterm infants was not significantly higher than that in full term infants. DTP vaccine is immunogenic and safe in preterm infants when the series is initiated at 2 months after birth, and this study supports the current recommendation of the American Academy of Pediatrics.