Objective: Our purpose was to determine whether the functional genetic polymorphisms of the β₂-adrenergic receptor (β₂AR) that result in changes in amino acid residues 16 and 27 are associated with preterm delivery. Study Design: A case-control study comparing the distribution of β₂AR genotype between 251 Hispanic women delivered at term and 28 Hispanic women delivered preterm. Preterm delivery was defined as spontaneous onset of labor resulting in delivery before 37 weeks of gestation, in a singleton pregnancy, with no apparent etiology for preterm labor and delivery. Genomic DNA was isolated from peripheral blood, and β₂AR alleles were identified by established techniques. Results: Only one woman (4%) with preterm labor was homozygous for Arg16 versus 79 (31%) in the control group (P = .01, odds ratio 0.08). There was no association of preterm labor with genotype at position 27. Conclusion: Our data demonstrate that homozygosity for Arg16, which in vitro is associated with decreased down-regulation of the β₂AR, protects from preterm delivery. (Am J Obstet Gynecol 2002;187:1294-8.)