The present prospective study assessed the impact of birth weight (BW) and postnatal weight gain on blood pressure and metabolic profile during the first 5 years of life. One hundred thirty-nine newborns (63 women) born at term after uncomplicated pregnancies and in the absence of perinatal illness were included. Subjects were divided according to size at birth in small, appropriate, and large for gestational age. After the initial evaluation on the second day of life, infants were followed up at 6 months and 2 and 5 years. Anthropometric parameters and blood pressure were measured at each visit and metabolic assessment was performed at 5 years of age. Among the BW groups, mothers did not differ in terms of age, smoking, and weight gain during pregnancy. BW was a positive determinant of systolic blood pressure at birth. Afterward, current weight was the strongest determinant, becoming significant at 2 years of age and progressively increasing in influence. At 5 years insulin, the homeostasis model assessment index and triglycerides were dependent on BW, current weight, and postnatal weight gain. In addition, BW was positively associated with high-density lipoprotein-cholesterol and inversely so to uric acid. A positive relationship among insulin, blood pressure values, and uric acid was observed even early in life. In conclusion, the acceleration of early infant weight gain may aggravate the effects of low BW. Multiple interactions between hemodynamic and metabolic parameters foreshadow the clustering of cardiometabolic risk factors later in life.