This retrospective observational study compared pregnancy outcomes based on mode of delivery in women with homozygous sickle cell disease (HbSS) to women without (HbAA) using delivery records of 48,600 parturients between January 1992 and January 2020. Fisher's exact tests and Mann-Whitney's test were used to analyse variables based on sickle cell status. Vaginal delivery and HbSS were more associated with labour induction/augmentation (AOR = 2.4, (0.7-7.8)), intrapartum complications (AOR = 2.6, (0.5-14)), postpartum haemorrhage (AOR = 2.8 (0.5-15.2)) and postpartum infections (AOR = 9.6 (1.7-54.4)). Caesarean delivery resulted in more postpartum infections in the HbSS group (AOR = 23.6 (0.9-638.4)). Vaginal delivery in HbSS resulted in more intrapartum complications and postpartum haemorrhage but caesarean delivery greatly increased the risk of postpartum infections and hypertensive disorders. Sickle cell disease (SCD) did not confer increased risk of adverse perinatal outcomes regardless of mode of delivery.Impact StatementWhat is already known on this subject? Women with homozygous sickle cell disease (SCD) are at an increased risk of postpartum infections, undergoing caesarean delivery, admission to the neonatal intensive care unit and overall perinatal mortality when compared to women with normal haemoglobin genotype. Comparisons have been made between homozygous SS disease and haemoglobin SC disease revealing higher rates of maternal and foetal morbidity in both groups.What do the results of this study add? Studies comparing maternal and foetal morbidity based on mode of delivery are lacking. To our knowledge, this study is the first examine maternal and perinatal outcomes in women with SCD undergoing vaginal and abdominal delivery compared to women with normal haemoglobin. We found that vaginal delivery in SCD is associated with more postpartum haemorrhage and caesarean delivery was linked to more hypertensive disorders and postpartum infections then compared to women with normal haemoglobin. Converse to other reports, there was no difference in perinatal outcomes based on mode of delivery.What are the implications of these findings for clinical practice and/or further research? Caesarean delivery and SCD greatly increased the risk of postpartum infections and hypertensive disorders but did not confer a higher risk of postpartum haemorrhage. There were more maternal deaths in SCD women who underwent caesarean vs. vaginal delivery and this requires further study to determine the pregestational predictors of adverse outcomes. Women with SCD who achieve a successful primary vaginal delivery may have reduced risk of complications in subsequent pregnancies, possibly comparable to women without the disease.