Context: Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results. Objective: The aim of the present study was to compare the effectiveness of 3 lifestyle interventions [healthy eating (HE), physical activity (PA), and both HE and PA (HE+PA)] with usual care (UC) in reducing GDM risk. Design: The present study was a multicenter randomized controlled trial conducted from 2012 to 2014 [the DALI (Vitamin D and lifestyle intervention for GDM prevention) lifestyle study]. Setting: The study occurred at antenatal clinics across 11 centers in 9 European countries. Patients: Consecutive pregnant women at ,20 weeks of gestation with a body mass index (BMI) of 29 kg/m2 and without GDM using the International Association of Diabetes and Pregnancy Study Group criteria (n = 436). For the intervention, women were randomized, stratified by site, to UC, HE, PA, or HE+PA. The women received 5 face-to-face and#4 telephone coaching sessions using the principles of motivational interviewing. A gestational weight gain (GWG) ,5 kg was targeted. The coaches received standardized training and an intervention toolkit tailored to their culture and language. Main Outcome Measures: The endpoints were the GWG at 35 to 37 weeks and the fasting glucose and insulin sensitivity [homeostasis model assessment insulin resistance (HOMA-IR)] at 24 to 28 weeks. Results: We randomized 108 women to HE+PA, 113 to HE, 110 to PA, and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially lessGWGthan did the controls (UC) by 35 to 37 weeks (22.02; 95% confidence interval, 23.58 to 20.46 kg). Despite this reduction, no improvements were seen in fasting or postload glucose levels, insulin concentrations, or HOMA-IR. The birthweights and large and small for gestational age rates were similar. Conclusions: The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycemia. Thus, lifestyle changes alone are unlikely to prevent GDM among women with a BMI of 29 kg/m2.