Abstract Study question The purpose of this study is to compare obese and non-obese women with multiple pregnancies to determine the effects on pregnancy, delivery, and neonatal outcomes. Summary answer Obesity and multiple gestations are independent risk factors for adverse obstetric outcomes. Combined, obesity in multiple gestation increases risk of maternal, delivery, and neonatal complications. What is known already Obesity is a pandemic and multiple pregnancies are a known consequence of assisted reproductive technologies. Obese women (body mass index [BMI] >30kg/m2) are at higher risk of hypertensive disorders, gestational diabetes, fetal growth complications, stillbirth, preterm birth, labour complications, caesarean deliveries, wound infection, venous thromboembolism, and adverse neonatal outcomes. Multiple gestation is associated with greater obstetric risks, including miscarriage, preterm birth, gestational diabetes, hypertensive disorders, operative delivery, postpartum hemorrhage, congenital anomalies, and fetal growth restriction. The combined effects are not well-established. Study design, size, duration We conducted a retrospective population-based study utilizing data collected between 2004 and 2014 inclusively, from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. We evaluated deliveries using the international classification of diseases [ICD], ninth edition, clinical modification codes for delivery-related discharge diagnosis and birth-related procedural diagnosis. All women with a diagnosis of multiple pregnancies were selected. They were subsequently divided based on the ICD-9 code for obesity. A total of 137,303 multiple pregnancies were analyzed. Participants/materials, setting, methods Within the 137,303 multiple pregnancies, 130,542 (95%) were non-obese, while 6,761 (5%) were obese. An initial analysis was performed to identify the prevalence of obesity in women with multiple pregnancies. We then compared baseline clinical and demographic characteristics between women with obesity to those without obesity using chi-squared tests. Subsequently, binary logistic regression analyses were conducted to explore comparisons between the obese and non-obese groups while adjusting for the potential confounding effects. Main results and the role of chance Over the 11-year study period, there was a statistically significant increase in prevalence of obesity for women with multiple gestations (p < 0.0001). The obese group was at higher risk of pregnancy-induced hypertension (adjusted odd’s ratio [aOR]=1.89, 95% confidence interval [CI]=1.77-2.02), gestational hypertension (aOR=1.84, CI = 1.65-2.05), preeclampsia (aOR=1.68, CI = 1.55-1.81), preeclampsia or eclampsia superimposed on pre-existing hypertension (aOR=1.86, CI = 1.58-2.20), gestational diabetes mellitus (aOR=2.65, CI = 2.44-2.87), and placenta previa (aOR=0.57, CI = 0.39-0.85). They were more likely to have preterm premature rupture of membranes (aOR=1.19, CI = 1.06-1.34), chorioamnionitis (aOR=1.24, CI = 1.03-1.51), caesarean sections (aOR=1.28, CI = 1.18-1.38), wound complications (aOR=1.65, CI = 1.31-2.08), and transfusions (aOR=0.77, CI = 0.67-0.89). They were less likely to have small for gestational age neonates (aOR=0.88, CI = 0.79-0.97), though more likely to have neonates with congenital anomalies (aOR=1.56, CI = 1.16-2.10). Conversely, for certain factors, the outcomes were similar between obese and non-obese women with multiple gestation including rates of eclampsia (p = 0.07), abruptio placenta (p = 0.82), hysterectomy (p = 0.36), postpartum hemorrhage (p = 0.08), maternal death (p = 0.98), maternal infection (p = 0.10), deep vein thrombosis (p = 0.17), pulmonary embolism (p = 0.75), venous thromboembolism (p = 0.15), disseminated intravascular coagulation (p = 0.85) and intrauterine fetal demise (p = 0.52). Limitations, reasons for caution The database is retrospective and relies on hospitals reporting elevated body mass index, which may not always be consistently recognized, potentially resulting in an underestimation of the total number of obese women. However, this only stands to support the increased risks detected in this study as being legitimate. Wider implications of the findings We addresses a significant gap in the literature by simultaneously exploring the impacts of multiple pregnancies and maternal obesity on obstetric complications. This can guide clinical practice, encouraging single embryo transfer in obese women undergoing in-vitro fertilization and tailored care for obese patients with multiple pregnancies, anticipating the associated risks. Trial registration number not applicable