Growth during infancy appears to be an important determinant of cardiovascular disease and type 2 diabetes later in life. To specify which period in the first year of life is related to determinants of cardiovascular disease and type 2 diabetes in early adulthood and to investigate the association between tempo of first-year weight gain (>0.67 SDs) and these determinants. Observational study using longitudinal data collected in the Programming Factors for Growth and Metabolism (PROGRAM) study of 217 healthy participants, aged 18 to 24 years, including a relatively large sample of participants born small for gestational age and participants with short stature, performed at a medical center in The Netherlands between August 2004 and September 2007. The association of cardiovascular disease and type 2 diabetes with tempo of weight gain was assessed in a subgroup of 87 participants. Associations between periods of first-year growth and tempo of weight gain and determinants of cardiovascular disease and type 2 diabetes in early adulthood. Weight gain in the first 3 months of life was inversely associated with insulin sensitivity (beta, -0.223; 95% confidence interval [CI], -0.386 to -0.060) and serum high-density lipoprotein cholesterol level (beta, -0.053; 95% CI, -0.090 to -0.016) and positively associated with waist circumference (beta, 1.437; 95% CI, 0.066 to 2.808), acute insulin response (beta, 0.210; 95% CI, 0.024 to 0.395), ratio of total cholesterol to high-density lipoprotein cholesterol (beta, 0.052; 95% CI, 0.010 to 0.094), and level of triglycerides (beta, 0.066; 95% CI, 0.003 to 0.129) in early adulthood. Rapid weight gain during the first 3 months of life resulted in a higher percentage of body fat, more central adiposity, and reduced insulin sensitivity in early adulthood than when slower weight gain occurred during the entire first year. Rapid weight gain in the first 3 months of life is associated with several determinants of cardiovascular disease and type 2 diabetes in early adulthood.