- Objective The purpose of this study was to compare the performance of the transabdominal versus the transvaginal route for the multifetal pregnancy reductions. Study design Two hundred ninety consecutive cases of multifetal pregnancy reduction were reviewed. Two hundred three reductions (70.0%) were done transabdominally; 75 cases (25.9%) were done transvaginally, and 12 cases (4.1%) used both routes. The indications for the transvaginal route were extreme obesity, abdominal scars, or if the lower fetus could not be reached transabdominally. Two hundred seventy-one women were delivered of live born babies after 24 weeks (group 1). Nineteen cases had pregnancy losses ≤24 weeks (group 2). Results The complete pregnancy loss rate was 6.5% (19/290 cases). Total pregnancy loss rates of multifetal pregnancy reduction were 3.5% (7/203 reductions) for the transabdominal route and 13.3% (10/75 reductions) for the transvaginal route (P = .004). Overall pregnancy losses were 4.8% for starting with twins, 6.6% for starting with triplets, 1.8% for starting with quadruplets, 14.3% for starting with quintuplets, and 14.3% with starting numbers of ≥6 fetuses. For finishing numbers, total pregnancy losses were 5.1% for ending with a singleton infant, 6.6% for ending with twins, and 0% for ending with triplets. Significant differences in complete pregnancy loss were observed between transabdominal and transvaginal routes for starting with triplets (2.7% for transabdominal versus 16.7% for transvaginal; P = .006) and for finishing with a single fetus (0% for transabdominal versus 20% for transvaginal; P < .004). Conclusion The multifetal pregnancy reduction success rate was higher with the transabdominal route compared with the transvaginal route. Significant differences in favor of the transabdominal route were observed for starting with triplets or finishing with a single fetus. The transvaginal route should be reserved only for cases in which the transabdominal approach is hard or impossible to perform. The performance of the procedure at 12 to 13 weeks of gestation enables structural evaluation of the fetuses before reduction.