Objective: To compare the differences in gestational complications, adverse pregnancy outcomes, and soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) levels between singleton pregnancies conceived via assisted reproductive technology (ART) and natural conception. Methods: This prospective study enrolled 547 pregnant women with clinical singleton pregnancies achieved through ART as the ART group (n=547). Based on baseline balance principles, 1,094 naturally conceived singleton pregnant women registered at our hospital’s obstetrics department during the same period were matched at a 1∶2 ratio as the control group (n=1,094). The gestational complications, pregnancy outcomes, and the sFlt-1/PLGF ratio were compared between the two groups. Results: The incidence of gestational diabetes mellitus, gestational hypertension, preeclampsia, postpartum hemorrhage, and fetal distress in the ART group were higher than those in the control group (P<0.05). The rates of cesarean section, fetal growth restriction, preterm birth, and low birth weight were higher in the ART group (P<0.05). Serum PLGF levels were lower, while sFlt-1 levels and the sFlt-1/PLGF ratio were higher in the ART group compared to the control group (P<0.05). Conclusion: Singleton pregnancies conceived through ART demonstrate higher risks of gestational complications and adverse outcomes compared to naturally conceived pregnancies, necessitating tailored management spanning pre-conception, prenatal, and postnatal stages to optimize maternal and neonatal outcomes.