Background: This study was undertaken with the objective of comparing efficacy and safety for two different regimens using misoprostol for induction of labour. Methods: The study was set in two different hospitals in the region of Zeeland, Denmark, and designed as a prospective cohort study. Nulliparous women with unripe cervix, eligible for vaginal delivery and medical induction of labour were included. Exclusion criteria were a previous uterine scar, suspicion of growth restriction of the fetus and prelabour rupture of membranes. One department used 25 mcg oral misoprostol tablets and the other department used 200 mcg slow-release misoprostol vaginal insert, for induction of labour. Primary outcomes were predefined as frequency of cesarean section, tachysystole and delivery within 24 h. Secondary outcomes were: time from induction to delivery, use of additional methods for induction, postpartum hemorrhage, anal sphincter rupture, epidural, pyrexia (rectal temperature > 38.5 °C), prolonged rupture of membranes, and use of tocolysis. Results: No significant differences in women achieving vaginal delivery was found. However, a significantly increased risk of tachysystole for the vaginal administration route was observed; 28.4% compared with 2.3%. There were no events of serious neonatal asphyxia. Half of the women induced with vaginal insert delivered within 24 h, compared with 16.8% of the women induced with oral misoprostol. Conclusions: Induction with vaginal slow-release misoprostol leads to quicker delivery with an increased risk of tachysystole but with similar perinatal outcomes and rates of cesarean sections. Low-dose oral misoprostol appears to be safe, however it leads to an increased use of secondary methods and a tendency of more intrapartum pyrexia. Trial registration: Clinicaltrials.gov ID: NCT02693587 on February 262,016. EudraCT number 2020-000366-42 on 23 January 2020, retrospectively registered.