Background:  The development of safe and effective techniques for second‐trimester abortion (associated or not with fetal death) has become a major clinical challenge.
Aims:  To compare the efficacy and safety of sublingual versus vaginal misoprostol for mid‐trimester pregnancy termination.
Methods:  We conducted a meta‐analysis of published randomised controlled trials that compared sublingual and vaginal routes. Primary outcome measures were complete abortion rate at 24 and 48 h and induction–abortion interval, and the secondary outcome measures were side effects and patients’ preference for the route. Pooled risk ratios were calculated for categorical variables, and continuous variables were compared by means of weighted mean differences.
Results:  Both routes’ efficacy was similar following 24 h of treatment (pooled RR 1.04, 95% CI 0.93–1.7). Successful induction percentage after 24 h was significantly higher in nulliparous women with vaginal misoprostol (pooled RR 0.78; 95% CI 0.71–0.87). The efficacy after 48 h was significantly greater with vaginal misoprostol in the general population (pooled RR 0.96; 95% CI 0.93–0.99) and in nulliparous women (pooled RR 0.89; 95% CI 0.86–0.95). The sublingual route shortened the induction‐fetal expulsion interval (WMD −4.54, 95% CI −8.03 to −1.05) and was the route preferred among women. No statistically significant differences between treatment groups were observed for placental retention or for any side effect except for fever, which was more common in the vaginal group.
Conclusions:  Sublingual and vaginal misoprostol are safe and effective for mid‐trimester pregnancy termination. The differences obtained between both routes probably do not have clinical consequences.