Context: Obesity management prior to infertility treatment remains a challenge.To date, results from randomized clinical trials involving weight loss by lifestyle interventions have shown no evidence of improved live birth rate. Objective: This work aimed to determine whether pharmacologic-weight-loss intervention before in vitro fertilization and embryo transfer (IVF-ET) can improve live birth rate among overweight or obese women. Methods: We conducted a randomized, double-blinded, placebo-controlled trial across 19 reproductive medical centers in China, from July 2017 to January 2019. A total of 877 infertile women scheduled for IVF who had a body mass index of 25 or greater were randomly assigned to receive orlistat (n = 439) or placebo (n = 438) treatment for 4 to 12 weeks.The main outcome measurement was the live birth rate after fresh ET. Results: The live birth rate was not significantly different between the 2 groups (112 of 439 [25.5%] with orlistat and 112 of 438 [25.6%] with placebo; P= .984). No significant differences existed between the groups asto the rates of conception, clinical pregnancy, or pregnancy loss. A statistically significant increase in singleton birth weight was observed after orlistat treatment (3487.50 g vs 3285.17 g in the placebo group; P= .039).The mean change in body weight during the intervention was -2.49 kg in the orlistat group, as compared to -1.22 kg in the placebo group, with a significant difference (P= .005). Conclusion: Orlistat treatment, prior to IVF-ET, did not improve the live birth rate among overweight or obese women, although it was beneficial for weight reduction.