Background and objectives Guidelines and indications for exchange transfusion in haemolytic disease of the foetus and newborn (HDFN) have changed drastically in the past decades, causing a decline in exchange transfusion rate. This study aims to evaluate the incidence of exchange transfusions (ETs) in neonates with Rh‐mediated HDFN over the past 20 years at our centre, and report potentially ET‐related complications as well as indicators for bilirubin encephalopathy. Material and methods In this observational study, 438 neonates were included with HDFN, born ≥ 35 weeks gestational age at the Leiden University Medical Centre between January 2000 and July 2020. The incidence of ET and procedure‐related complications were assessed in three consecutive time periods determined by changes in guidelines and indications for ET. Results The incidence of ET in our centre declined from (104/156) 67% (time period 2000–2005), to (39/181) 22% (2006–2015) and to (10/101) 10% (2015–2020, p < 0·001). The maximum bilirubin levels in neonates after birth increased from 13·6 mg/dL (or 233 μmol/L), to 15·0 mg/dL (257 μmol/L) and to 15·3 mg/dL (263 μmol/L). The incidence of complications associated with the use of ET (including sepsis, haematologic disorders and respiratory failure) remained stable throughout the years, and no neonates died during the study period. Conclusion Exchange transfusion incidence declined significantly over the past two decades. Decrease in ET incidence, and concomitant decrease in exposure and expertise, was not associated with an increase in procedure‐related complications.

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