We estimated the 10-year incidence of major weight gain (a gain in body mass index of greater than or equal to 5 kg/m2 and overweight (a body mass index of greater than or equal to 27.8 for men and greater than or equal to 27.3 for women) in US adults using data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Persons aged 25 to 74 years at baseline were reweighed a decade after their initial examination (men, 3727; women, 6135). The incidence of major weight gain was twice as high in women and was highest in persons aged 25 to 34 years (men, 3.9%; women, 8.4%). Initially overweight women aged 25 to 44 years had the highest incidence of major weight gain of any subgroup (14.2%). For person not overweight at baseline (men, 2760; women, 4295), the incidence of becoming overweight was similar in both sexes and was highest in those aged 35 to 44 years (men, 16.3%; women, 13.5%). We conclude that obesity prevention should begin among adults in their early 20s and that special emphasis is needed for young women who are already overweight.