Rapid early weight gain has been associated with increased risk of obesity and cardiometabolic alterations, but evidence in low and middle-income countries is inconclusive. We evaluated the relation between relative weight gain from 1 to 48 mo with adiposity and cardiometabolic risk factors at 4-5 y of age, and determined if adiposity is a mediator for cardiometabolic alterations. We studied 428 Mexican children with anthropometric and blood pressure (BP) information from birth to 5 y of age from POSGRAD (Prenatal Omega-3 fatty acid Supplementation and child GRowth And Development), of whom 334 provided measures of adiposity and cardiometabolic risk markers at 4 y. We estimated relative weight gain by means of conditional weight-for-height z scores for the age intervals 1-6, 6-12, 12-24, and 24-48 mo. Associations between relative weight gain and adiposity and cardiometabolic risk markers (lipid profile, triglycerides, insulin, glucose, and BP) were analyzed by multivariate multiple linear models and path analysis. A 1-unit increase in conditional weight-for-height z score within each age interval was positively associated with adiposity at 5 y, with coefficients of 0.43-0.89 for body mass index (BMI) z score, 1.08-3.65 mm for sum of skinfolds, and 1.21-3.87 cm for abdominal circumference (all P