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Objective To evaluate the effects of postpartum diet and lifestyle intervention on gestational diabetes (GDM) women with different genetic risk scores (GRS). Methods Based on an established randomized controlled trial (RCT) evaluating the effects of a postpartum diet and lifestyle intervention between August 2009 and September 2013, women with previous GDM and non-diabetes postpartum were recruited. Information at baseline and follow-up survey after 1-year intervention were collected, including fasting blood glucose (FPG), 2-hour blood glucose (2hPG), total cholesterol (TC), body fat, waist circumference, dietary fiber intake>20 g/d, and exercise> 30 min/d and other indicators. The height and body weight were recorded, and the body mass index (BMI) was calculated. After 1-year intervention, percentage reduction in initial weight, and changes in 2hPG, TC, weight, BMI, waist circumference and body fat percentage were calculated. We detected 11 postpartum type 2 diabetes mellitus (T2DM)-related single nucleotide polymorphisms (SNP) which were previously validated, and calculated the individual′s comprehensive GRS. Patients were divided into low genetic risk group (GRS<10.00) and high genetic risk group (GRS≥10.00) according to the median of GRS. In the low and high genetic risk groups, patients were divided into lifestyle intervention group and control group respectively. The t test or χ2 test were used to compare the indicators between the intervention and control group. Results A total of 675 patients were enrolled in the study, including 292 patients with low genetic risk (142 in the intervention group and 150 in the control group), and 383 patients with high genetic risk (188 in the intervention group and 195 in the control group), respectively. Among patients with low genetic risk, compared with control group, patients in the intervention group had a higher rate of dietary fiber intake>20 g/d (P=0.037), a lower rate of abnormal blood glucose (P=0.012), and better changed 2hPG and TC (both P<0.05). Among patients with high genetic risk, compared with control group, patients in the intervention group had a higher rate of exercise>30 min/d (P=0.003), better changed fasting insulin (P=0.038), and the changes in weight, percentage in weight change BMI, waist circumference and body fat percentage were larger (all P<0.05). Conclusions The postpartum diet and lifestyle intervention were relatively effective for GDM patients with different genetic risks. GDM patients with low genetic risk had increased dietary fiber intake, improved blood glucose and lipid levels, and lower risk of abnormal blood glucose. GDM patients with high genetic risk had larger changes in weight, BMI, waist circumference and body fat percentage, and better insulin improvement after comprehensive intervention. [ABSTRACT FROM AUTHOR]