We have previously shown that cardiorespiratory fitness predicts increasing fat mass during growth in white and African-American youth, but limited data are available examining this issue in Hispanic youth. Study participants were 160 (53% boys) overweight (BMI>or=85th percentile for age and gender) Hispanic children (mean+/-s.d. age at baseline=11.2+/-1.7 years). Cardiorespiratory fitness, assessed by VO2max, was measured through a maximal effort treadmill test at baseline. Body composition through dual-energy X-ray absorptiometry and Tanner stage through clinical exam were measured at baseline and annually thereafter for up to 4 years. Linear mixed models were used to examine the gender-specific relationship between VO2max and increases in adiposity (change in fat mass independent of change in lean tissue mass) over 4 years. The analysis was adjusted for changes in Tanner stage, age, and lean tissue mass. In boys, higher VO2max at baseline was inversely associated with the rate of increase in adiposity (beta=-0.001, P=0.03); this effect translates to a 15% higher VO2max at baseline resulting in a 1.38 kg lower fat mass gain over 4 years. However, VO2max was not significantly associated with changes in fat mass in girls (beta=0.0002, P=0.31). In overweight Hispanic boys, greater cardiorespiratory fitness at baseline was protective against increasing adiposity. In girls however initial cardiorespiratory fitness was not significantly associated with longitudinal changes in adiposity. These results suggest that cardiorespiratory fitness may be an important determinant of changes in adiposity in overweight Hispanic boys but not in girls.