Objective: Pre-pregnancy obesity and gestational diabetes mellitus (GDM) are increasingly prevalent independent risk factors for maternal and infant morbidities. However, there is a paucity of information on their joint effects on health outcomes and healthcare costs., Methods: A population-based retrospective cohort study was conducted in Florida using a validated statewide database covering 1,057,647 infants born between 2004 and 2009. Using generalized linear modeling, joint associations between levels of pre-pregnancy body mass index (BMI) and GDM and maternal complications of pregnancy, adverse birth outcomes, and healthcare costs were examined. The relative excess risk due to interaction was used to describe the direction and magnitude of the BMI-GDM interaction on the additive scale., Results: Increasing pre-pregnancy BMI conferred increasing odds of adverse consequences, as did GDM, and the BMI-GDM interaction was greater than additive for 9 of 14 outcomes. The cost for infants born to women with GDM/obesity-III was 34% higher during the first year compared with those born to women with normal BMI and without GDM. The costs of maternal and infant inpatient care associated with overweight/obesity and GDM totaled over $351 million., Conclusions: These findings provide further evidence of the importance of lifestyle modifications to decrease rates of obesity and risk factors from GDM., (© 2015 The Obesity Society.)