OBJECTIVETo systematically review published randomized controlled trials (RCTs) to compare the safety and efficacy of 25 μg versus 50 μg of intravaginal misoprostol for cervical ripening and labor induction.DATA SOURCESWe supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify RCTs of misoprostol for cervical ripening and labor induction, which compared repeated doses of 25 μg and 50 μg.STUDY SELECTIONWe evaluated, abstracted data, and assessed the quality of RCTs to compare the safety and efficacy of 25 μg versus 50 μg of intravaginal misoprostol for cervical ripening and labor induction.TABULATION, INTEGRATION, AND RESULTSFive RCTs met inclusion criteria for meta-analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for each outcome (random- and fixed-effects models). In addition, we aggregated the results of two separate studies, permitting an indirect comparison of the two doses being analyzed. In the meta-analysis, tachysystole and hyperstimulation syndrome appear to occur less frequently among women who received 25 μg of misoprostol than with 50 μg. However, neonatal outcomes appear to be comparable with the two doses. Regarding efficacy, use of the 50-μg dose was associated with a shorter interval to vaginal delivery, greater proportion of deliveries within 24 hours, and less frequent need for oxytocin augmentation. The indirect comparison of two studies yielded similar results.CONCLUSIONPublished data indicate that intravaginal misoprostol at doses of 50 μg for cervical ripening and labor induction is more efficacious but it is unclear whether it is as safe as the 25-μg dose.