To examine whether maternal caffeine consumption is associated with the risk of spontaneous abortion, we analyzed data from a population-based prospective study. The study population comprised 575 women delivering singleton livebirths and 75 women who had spontaneous abortions. The subjects were predominantly white, middle-class women enrolled before pregnancy. Study participants were traced to delivery of a liveborn, singleton infant or a spontaneous abortion. Of the 71 women who did not experience nausea, 29.6% had a spontaneous abortion, compared with 7.2% of 514 women who did experience nausea. Maternal caffeine consumption before pregnancy, or in women without nausea, did not increase the risk of spontaneous abortion, whereas maternal caffeine consumption during the first trimester after nausea started might increase risk of spontaneous abortion (risk ratio = 5.4, 95% confidence interval = 2.0–14.6 for caffeine consumption ≥300 mg per day compared with <20 mg per day). These results suggest that maternal caffeine consumption during pregnancy may influence fetal viability in women with nausea.