Maternal overweight or obesity has been associated with metabolic syndrome through 1 year postpartum, but it remains unknown whether a culturally-modified, motivationally-targeted, and individually-tailored Lifestyle Intervention could improve postpartum cardiometabolic health among Hispanic women with overweight or obesity. Proyecto Mamá was a randomized controlled trial conducted in Western Massachusetts from 2014 to 2020 in which Hispanic women with overweight/obesity were randomized to a Lifestyle Intervention (LI) involving diet and exercise or to a comparison Health and Wellness Intervention (HW). Biomarkers of cardiovascular risk (i.e., lipids, C-reactive protein) and insulin resistance (fasting insulin, glucose, HbA1c, homeostasis model assessment [HOMA-IR], leptin, adiponectin) were measured at baseline (early pregnancy), mid-pregnancy, and 6 weeks, 6 months, and 12 months postpartum. Generalized linear mixed effect models were used to evaluate differences in the change in biomarkers over the course of postpartum follow-up time. In intent-to-treat analyses among eligible women (LI; n=51, HW; n=58) there were no significant differences in changes in biomarkers of CVD risk or insulin resistance over the postpartum year; for example, the intervention effect for total cholesterol was 6.98 (SE: 6.36, p=0.27) and for HbA1c was -0.01 (SE: 0.4, p=0.85). In pooled analyses, regardless of intervention arm, women who participated in any vigorous activity had less of an increase in HbA1c (intervention effect = -0.17, SE: 0.05, p=0.002) compared to those with no vigorous activity, and similarly beneficial associations with other cardiovascular risk biomarkers (p<0.05). Women who participated in vigorous activity, regardless of their assigned intervention arm, had more favorable changes in biomarkers of insulin resistance.