Objective: To identify risk factors associated with placenta accreta in a large cohort study. Methods: Data for this study came from the Taiwan Down Syndrome Screening Group, an ongoing project on feasibility of serum screening in an Asian population. Women who had serum screening for Down syndrome at 14–22 weeks’ gestation using alpha-fetoprotein (AFP) and free β-hCG between January 1994 and June 1997, and delivered in the same institution, were included (n = 10,672). Those who had multiple gestations (n = 200), overt diabetes (n = 11), or fetal malformations (n = 101) were excluded. If a woman was involved more than once, one randomly selected pregnancy was included in the analysis (n = 9349). Twenty-eight pregnancies were complicated by placenta accreta, diagnosed by clinical presentation (n = 26) or histologic confirmation (n = 2). Multiple logistic regression with adjustment for potentially confounding variables was used to identify independent risk factors for placenta accreta. Results: Women who had placenta previa (odds ratio [OR] 54.2; 95% confidence interval [CI] 17.8, 165.5) and second-trimester serum levels of AFP and free β-hCG greater than 2.5 multiples of the median (OR 8.3; 95% CI 1.8, 39.3 and OR 3.9; 95% CI 1.5, 9.9, respectively), and were 35 years and older (OR 3.2; 95% CI 1.1, 9.4) were at increased risk of having placenta accreta. Conclusion: Risk factors for placenta accreta include placenta previa, abnormally elevated second-trimester AFP and free β-hCG levels, and advanced maternal age.