We sought to determine the relationship of fibroids to pregnancy loss in a prospective cohort in which fibroid status was uniformly documented in early pregnancy. Participants had an intake interview, transvaginal ultrasonography, computer-assisted telephone interview, and follow-up assessment of outcomes. We recruited diverse participants for the Right From the Start study from 8 metropolitan areas in 3 states in the United States during 2000-2012. Participants were at least 18 years of age, trying to become pregnant or at less than 12 weeks' gestation, not using fertility treatments, fluent in English or Spanish, and available for telephone interviews. Miscarriage was defined as loss before 20 weeks' gestation. Fibroid presence, number, type, and volume were assessed using standardized ultrasonography methods. We used proportional hazards models to estimate associations. Among 5,512 participants, 10.4% had at least 1 fibroid, and 10.8% experienced a miscarriage. Twenty-three percent had experienced a prior miscarriage and 52% prior births. Presence of fibroids was associated with miscarriage in models without adjustments. Adjusting for key confounders indicated no increase in risk (adjusted hazard ratio = 0.83, 95% confidence interval: 0.63, 1.08). No characteristic of fibroids was associated with risk. Prior evidence attributing miscarriage to fibroids is potentially biased. These findings imply that surgical removal of fibroids to reduce risk of miscarriage deserves careful scrutiny.