ObjectiveIn this study, we aim to evaluate trends in the condition of fetuses and neonates with hemolytic disease at the time of first intrauterine transfusion (IUT) and at birth, in relation to routine first‐trimester antibody screening, referral guidelines, and centralization of fetal therapy.MethodWe conducted a 30‐year cohort study including all women and fetuses treated with IUT for red cell alloimmunization at the Dutch national referral center for fetal therapy.ResultsSix hundred forty‐five fetuses received 1852 transfusions between 1 January 1987 and 31 December 2016. After the introduction of routine first‐trimester antibody screening, the hydrops rate declined from 39% to 15% (OR 0.284, 95% CI, 0.19‐0.42, P < 0.001). In the last time cohort, only one fetus presented with severe hydrops (OR 0.482, 95% CI, 0.38‐0.62, P < 0.001). Infants are born less often <32 weeks (OR 0.572, 95% CI, 0.39‐0.83, P = 0.004) and with higher neonatal hemoglobin (P < 0.001). Neonatal hemoglobin was positively independently associated with gestational age at birth, fetal hemoglobin, and additional intraperitoneal transfusion at last IUT.ConclusionSevere alloimmune hydrops, a formerly often lethal condition, has practically disappeared, most likely as a result of the introduction of routine early alloantibody screening, use of national guidelines, and pooling of expertise in national reference laboratories and a referral center for fetal therapy.