Background: The purpose of the present study was to evaluate the effectiveness of a misoprostol vaginal insert as an induction-of-labor (IOL) agent in women with an unfavorable cervix (Bishop score < 2) in achieving vaginal delivery (VD) within 48 h, depending on the gestational week, with particular emphasis on the cesarean section (CS) percentage, intrapartum analgesia application and possible side effects, such as tachysystole ratio. Methods: In this retrospective observational study involving 6000 screened pregnant patients, 190 women (3%) fulfilled the study inclusion criteria and underwent vaginal misoprostol IOL. The pregnant women were collected into three groups: patients who delivered at up to 37 weeks of gestation (<37 Group)—42 patients; patients who delivered between 37 and 41 weeks of gestation (37–41 Group)—76 patients; and patients who delivered after 41 weeks of gestation (41+ Group)—72 patients. The outcomes included time to delivery and mode of delivery, rate of tachysystole, need for intrapartum analgesia, and need for oxytocin augmentation. Results: Most of the patients delivered vaginally (54.8% in <37 Group vs. 57.9% in 37–41 Group vs. 61.1% in 41+ Group). A total of 89.5% (170/190) of patients delivered within 48 h (<37 Group—78.6% vs. 37–41 Group—89.5% vs. 41+ Group—95.8%). Statistical significance was demonstrated for the increased rate of vaginal deliveries and shortened time to delivery in the 41+ weeks group (p= 0.0026 andp= 0.0038). The indications for cesarean section were as follows: abnormal CTG pattern vs. lack of labor progression: 42.1% vs. 57.9% in <37 Group, 59.4% vs. 40.6% in 37–41 Group and 71.4% vs. 28.6% in 41+ Group. Statistical significance was demonstrated for the increased rate of abnormal CTG patterns as cesarean section indications in the 41+ Group (p= 0.0019). The need for oxytocin augmentation in each group was: 35.7% in <37 Group vs. 19.7% in 37–41 Group vs. 11.1% in 41+ Group. Statistical significance was shown for decreased need for oxytocin augmentation in +41 Group (p= 0.0016). The need for intrapartum anesthesia, depending on the group, was: 78.6% in <37 Group vs. 82.9% in 37–41 Group vs. 83.3% in 41+ Group. Statistical significance was demonstrated for increased need for intrapartum anesthesia application during labor in +41 Group (p= 0.0018). The prevalence of hyperstimulation was similar in all three groups (4.8% vs. 7.9% vs. 5.6%p> 0.05). Conclusions: The misoprostol vaginal regimen for IOL used in our study is effective in achieving vaginal delivery within 48 h. In post-term women, the use of this regimen is characterized by an increased rate of vaginal deliveries, a shorter time to delivery and a lower need for oxytocin.