Objective Vaginal birth after a prior low transverse caesarean section (VBAC) is advocated as a safe and effective method to reduce the total caesarean section rate. However, the risk of uterine rupture has dampened the enthusiasm of practising clinicians for VBAC. Uterine rupture occurs more frequently in women receiving prostaglandins in preparation for the induction of labour. We hypothesised that similar to the cervix, prostaglandins induces biochemical changes in the uterine scar favouring dissolution, predisposing the uterus to rupture at the scar of the lower segment as opposed to elsewhere. Design We tested aspects of this hypothesis by investigating the location of uterine rupture associated with prostaglandins and compared it with the sites of rupture in the absence of prostaglandins. Settings Two North American University Hospitals.Population Twenty-six women with a prior caesarean section, experiencing uterine rupture in active labour.Methods Retrospective review of all pregnancies complicated by uterine rupture at two North American teaching hospitals from 1991 to 2000. Main outcome measure Site of the uterine rupture.Results Thirty-four women experienced rupture after a previous caesarean section with low transverse uterine incision. Ten of the women who ruptured (29%) received prostaglandins for cervical ripening (dinoprostone: n ¼ 8 or misoprostol: n ¼ 2) followed by either spontaneous contractions (n ¼ 3) or oxytocin augmentation during labour (n ¼ 7). In 16 women (47%), oxytocin alone was sufficient for the induction/augmentation of labour. Eight (23%) women ruptured at term before reaching the active phase of labour in the absence of pro-contractile agents or attempted VBAC. There were no differences among the groups in terms of age, body mass index, parity, gestational age, fetal weight or umbilical cord pH measurements. Women treated with prostaglandins experienced rupture at the site of their old scar more frequently than women in the oxytocin-alone group whose rupture tended to occur remote from their old scar (prostaglandins 90% vs oxytocin 44%; OR: 11.6, 95% CI: 1.2 -114.3). Conclusion Women in active labour treated with prostaglandins for cervical ripening appear more likely to rupture at the site of their old scar than women augmented without prostaglandins. We propose that prostaglandins induce local, biochemical modifications that weaken the scar, predisposing it to rupture.