Objective: The objective of this study was to estimate the efficiency of first-trimester a disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), uterine artery Doppler, and maternal characteristics in the prediction of preterm birth (PTB). Methods: This was a prospective cohort study of patients presenting for first-trimester aneuploidy screening. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices were calculated. The primary outcome was PTB <34weeks' gestation, and the secondary outcome was PTB <37weeks' gestation. Logistic regression was used to model the prediction of PTB using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics, individually and in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves were compared between models. Results: Of 578 patients, 36 (6.2%) delivered <34weeks, and 78 (13.5%) delivered <37weeks. For a 20% fixed false positive rate, ADAM12, PAPP-A, and uterine artery Doppler identified 58%, 52%, and 62% of patients with PTB <34weeks and 42%, 48%, and 50% of patients with PTB <37weeks, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. Conclusion: First-trimester ADAM12, PAPP-A, and uterine artery Doppler are each modestly predictive of PTB; however, combinations of these parameters do not further improve their screening efficiency.