Minimal stimulation in vitro fertilization (mini-in vitro fertilization) is an alternative in vitro fertilization treatment protocol that may reduce ovarian hyperstimulation syndrome, multiple pregnancy rates, and cost while retaining high live birth rates.We performed a randomized noninferiority controlled trial with a prespecified border of 10% that compared 1 cycle of mini-in vitro fertilization with single embryo transfer with 1 cycle of conventional in vitro fertilization with double embryo transfer.Five hundred sixty-four infertile women (<39 years old) who were undergoing their first in vitro fertilization cycle were allocated randomly to either mini-in vitro fertilization or conventional in vitro fertilization. The primary outcome was cumulative live birth rate per woman over a 6-month period. Secondary outcomes included ovarian hyperstimulation syndrome, multiple pregnancy rates, and gonadotropin use. The primary outcome was cumulative live birth per randomized woman within a time horizon of 6 months.Five hundred sixty-four couples were assigned randomly between February 2009 and August 2013 with 285 couples allocated to mini-in vitro fertilization and 279 couples allocated to conventional in vitro fertilization. The cumulative live birth rate was 49% (140/285) for mini-in vitro fertilization and 63% (176/279) for conventional in vitro fertilization (relative risk, 0.76; 95% confidence interval, 0.64-0.89). There were no cases of ovarian hyperstimulation syndrome after mini-in vitro fertilization compared with 16 moderate/severe ovarian hyperstimulation syndrome cases (5.7%) after conventional in vitro fertilization. The multiple pregnancy rates were 6.4% in mini-in vitro fertilization compared with 32% in conventional in vitro fertilization (relative risk, 0.25; 95% confidence interval, 0.14-0.46). Gonadotropin consumption was significantly lower with mini-in vitro fertilization compared with conventional in vitro fertilization (459 ± 131 vs 2079 ± 389 IU; P < .0001).Compared with conventional in vitro fertilization with double embryo transfer, mini-in vitro fertilization with single embryo transfer lowers live birth rates, completely eliminates ovarian hyperstimulation syndrome, reduces multiple pregnancy rates, and reduces gonadotropin consumption.