A higher incidence of preterm birth (PTB) and premature rupture of membranes (PROM) has been observed among women delivering male newborns compared with female newborns in different populations. Some authors have speculated that this higher incidence of PTB may be related to the relatively greater weight at lower gestational age of male newborns compared with female newborns. Others have suggested that the greater incidence of PTB and PROM is caused by an increased vulnerability to infection in women carrying males. To understand possible pathogenic factors leading to PTB further, we examined the association between PTB and infant gender in a cohort of North American women. In addition, incidences of PROM, chorioamnionitis, and postpartum endometritis were analyzed for women delivering males versus females. Overall, males were more likely than females to deliver at 33 to 36 weeks' gestation (OR = 1.21; 95% CI: 1.02-1.42). This increase in PTB among males was not accompanied by an increased number of males with low birthweight; rather, males were less likely than females to weigh between 2000 and 2499 gm (OR = 0.71; 95% CI: 0.60-0.84). The difference in PTB by gender could not be explained by an increased occurrence of PROM, chorioamnionitis, endometritis, or other infection-linked processes. Our findings suggest that shorter gestation in males in this population may be related to their relatively increased size and birthweight. Male gender-associated factors that predispose to infection-mediated preterm birth may play greater roles in populations at higher risk for reproductive tract infection during pregnancy.