Preterm birth, defined as birth prior to 37 completed weeks gestation, is a serious health concern. Despite advances in health care screening and interventions, the rate of preterm birth in the United States has risen more than 30 percent since 1981. In 2006, Menon and associates reported the first multilocus genetic interaction in three single nucleotide polymorphisms predictive of spontaneous preterm birth in a population of White mothers. A gene association study using a case-control design was conducted to determine whether the results of the Menon study were also true for Black women and their infants. The case group included 22 preterm mothers and 22 preterm infants. The control group included 106 term mothers and 108 term infants. Study variables included high-risk and low-risk genetic combinations of the three single nucleotide polymorphisms. Birth certificate applications were reviewed to determine subject eligibility. Blood samples obtained by hospital personnel were sent to a laboratory for genotyping. It was predicted that there would be no statistically significant difference in the occurrence of the high-risk genetic patterns in the preterm Black mothers or their infants. Data analysis suggested that the multilocus genetic combinations reported by Menon were not predictors for preterm birth in Black mothers or their infants. Further study is recommended to identify genetic variations predictive of preterm birth across ethnic groups.