The purpose of this article is to investigate the frequency of the tumor necrosis factor-alpha (TNF-alpha) -308 G/A single nucleotide polymorphism in women with intrauterine fetal death, preeclampsia, preterm delivery, and small-for-gestational-age (SGA) infants. In a prospective cohort study, DNA from 1652 consecutive pregnant women was analyzed for TNF-alpha -308 G/A by polymerase chain reaction. Women who developed at least 1 of the predefined pregnancy complications were used as cases and compared to women without pregnancy complications. Of 1652 women, 268 (16.2%) developed at least 1 pregnancy complication. TNF-alpha -308 G/A allele frequencies (G: 463/536 [86%] and A: 73/536 [14%] vs G: 2366/2768 [85%] and A: 402/2768 [15%], respectively; P = .6; odds ratio [OR], 0.93; 95% confidence interval [CI], 0.69-1.25) and genotype distributions (G/G+G/A: 259/268 [97%] and A/A 9/268 [3%] vs G/G+G/A: 1352/1384 [98%] and A/A 32/1384 [2%], respectively; P = .4; OR, 0.20; 95% CI, 0.002-14.81) were not significantly different between cases and controls. The authors observed no statistically significant difference in TNF-a -308 G/A genotype distributions comparing controls and women with intrauterine fetal death, preeclampsia, preterm delivery <34 weeks' gestation, preterm delivery >34 weeks' gestation, SGA infants <3rd percentile, and SGA infants of the 4th to 10th percentile. TNF-alpha -308 G/A is not a genetic marker for identifying women at increased risk of common pregnancy complications.