BACKGROUND: Antepartum haemorrhage of unknown origin (APHUO) is associated with preterm birth and perinatal mortality. AIM: To determine whether smoking beyond the first trimester of pregnancy was an independent risk factor for APHUO. METHODS: Rates of APHUO were compared between non-smokers and smokers, and non-smokers and ceased smokers. Participants were healthy nulliparous women recruited to the Screening for Pregnancy Endpoints (SCOPE) prospective cohort study in New Zealand, Australia, Ireland and United Kingdom. Logistic regression was used to compare adjusted odds ratio, 95% confidence intervals (OR, 95% CI) of APHUO between continued smokers and non-smokers, adjusting for possible confounders. RESULTS: Of the 3513 participants, 77.9% (n = 2737) were non-smokers, 10.6% (n = 371) ceased in the first trimester and 11.5% (n = 405) continued smoking beyond the first trimester. APHUO rates were higher in smokers than non-smokers (7.4%, n = 30 vs 4.5%, n = 122; P = 0.01), but there was no difference between ceased smokers and non-smokers (4.3%, n = 16 vs 4.5%, n = 122; P = 0.90). Smoking was no longer significantly associated with APHUO after adjustment for confounders (adjusted OR = 1.28, 95% CI 0.76–2.14), but vaginal bleeding in early pregnancy (adjusted OR = 2.98, 95% CI 2.12–4.18) and overweight/obesity (adjusted OR = 1.43, 95% CI 1.02–1.99) were independent risk factors. First trimester folic acid use was associated with a reduced risk (adjusted OR = 0.44, 95% CI 0.25–0.77). CONCLUSION: Smoking is not an independent risk factor for APHUO after adjustment for confounders, but other risk and protective factors have been identified. ; Marlies E.W.A. Van Altvorst, Eliza H.Y. Chan, Rennae S. Taylor, Louise C. Kenny, Jenny E. Myers, Gustaaf A. Dekker, Robyn A. North and Lesley M.E. McCowan