Objective: To determine the safety and efficacy of labor induction with low-dose vaginal prostaglandin E2 (PGE2) in grandmultiparous women with a previous cesarean delivery.Methods: We conducted a retrospective cohort study of 219 grandmultiparous women with a previous cesarean delivery (study group) who underwent induction of labor with low dose PGE2. These patients were compared to 1376 grandmultiparous women without a previous cesarean section (control group) who underwent induction of labor with low dose PGE2. The primary outcome was uterine rupture and secondary outcomes included mode of delivery, post-partum hemorrhage (PPH) and a low 5-min Apgar score (≤7).Results: One patient in the study group as well as one patient in the control group were diagnosed with uterine rupture (0.4% versus 0.07%). In the study group, vaginal delivery was achieved in 204 (93.16%) patients, whereas 15 (6.84%) patients had emergent cesarean delivery. Five minutes Apgar score ≤7 was recorded in two cases (0.9%) in the study group. Patients in the study group had a significantly higher rate of cesarean delivery (6.84%, versus 3.4%, respectively, p < 0.001) as well as operative vaginal delivery (4.56% versus 2% respectively, p < 0.05) compared to the control group. There were no significant differences between the groups regarding the rate of PPH (0.91% versus 0.90%, p = 0.2) or 5-min Apgar score ≤7 (0.91% versus 0.22%, p = 0.28).Conclusions: Low dose PGE2 is a relative safe method for induction of labor in grandmultiparous women with a previous cesarean section.