SummaryFactor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1·23/1000 was observed, but no significant association between FVL and pre‐eclampsia, intra‐uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante‐natal bleeding or intra‐partum or postpartum haemorrhage was observed. However, FVL was associated with birth‐weights >90th centile [odds ratio (OR) 1·81; 95% confidence interval (CI95) 1·04–3·31] and neonatal death (OR 14·79; CI95 2·71–80·74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy‐related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies.