In sickle cell disease (SCD), hydroxyurea lowers pain crises, acute chest syndrome, and blood transfusions. There were few studies on the effects of hydroxyurea administered for SCD during conception and pregnancy. In the clinical context, the Sickle Cell Disease Implementation Consortium collected self-reported pregnancy history, hydroxyurea use, and pregnancy outcomes in women with SCD. Among 1,285 women aged 18 to 45, 737 (57.4%) had 1,788 pregnancies (1,079 live births, 394 miscarriages, 40 stillbirths, 207 abortions, 48 current pregnancies, and 20 missing outcomes), with 241 (15.9%) live births, miscarriages, or stillbirths occurring while on hydroxyurea. In univariate analyses, having more than 3 pregnancies, having a severe sickle genotype, having a history of stillbirth or miscarriage, and having chronic kidney disease at the time of enrollment were all found to be covariates that were highly associated with a pregnancy ending in miscarriage or stillbirth. Using hydroxyurea during conception and pregnancy, but not just during conception, was linked to a higher risk of miscarriage or stillbirth (OR 2.21, 95% CI 1.40–3.47) after controlling for variables and other SCD severity criteria in multivariate analyses. In studies of live birth outcomes, hydroxyurea usage during conception and pregnancy was linked to full-term infants having a birth weight of fewer than 5.5 pounds (OR 2.98, 95% CI 1.09–7.38) but not to prematurity or significant medical issues at birth (OR 2.98, 95% CI 1.09–7.38). These data imply that hydroxyurea use might be safe until conception but that clinicians should continue to advise caution during pregnancy.