BACKGROUND No systematic empirical research exists addressing the question of optimal pregnancy termination method in second trimester pregnancies. OBJECTIVE The purpose of this study was to determine the efficacy and safety of intravaginal misoprostol and extraamniotic Foley catheter combination for second trimester pregnancy termination. METHODS A single center observational study was conducted in a total of 91 pregnancies. Women who met the termination of pregnancy criteria due to feto-maternal indications between 13 to 26 gestational weeks were included into the study. Study participants received intravaginal misoprostol in combination with Foley catheter (n = 46) or intravaginal misoprostol alone (n = 45). RESULTS The efficacy of intravaginal misoprostol and Foley catheter insertion combination was comparable to that of intravaginal misoprostol alone in terms of time to abortion/birth [median (95% Confidential Interval [95% CI]): 14.33 (11.33-17.25) hours and 12.08 (9.50-15.33) hours, respectively Hazard Ratio: 0.73, 95% CI: 0.47 to 1.12, p = 0.14 (log-rank)]. The only serious maternal event was uterine rupture observed in one woman in Foley combination group. CONCLUSIONS The combination of intravaginal misoprostol and extraamniotic Foley catheter for second trimester pregnancy termination does not provide additional efficacy.