BACKGROUNDStudies of the association between physical activity (PA) and weight maintenance have been inconsistent.METHODSWe prospectively examined the association between PA patterns and prevention of weight gain among 46,754 healthy premenopausal women, aged 25–43 years in 1989. Participants reported their PA and weight in 1989 and 1997. The primary outcome was gaining >5% of baseline weight by 1997 (62% of the population).RESULTSCompared with women who maintained <30 minutes/day of total discretionary activity over 8 years, women were less likely to gain weight if they sustained 30+ minutes/day (Odds Ratio OR=0.68, 95% confidence interval [CI] 0.64–0.73) or increased to 30+ minutes/day in 1997 (OR=0.64, 95%CI=0.60–0.68). Among women whose only reported activity was walking, risk of gaining weight was lower in those who sustained 30+ minutes/day over 8 years (OR=0.66, 95%CI=0.49–0.91), and brisk walking pace independently predicted less weight gain. For a 30 minutes/day increase between 1989 and 1997, jogging/running was associated with less weight gain than brisk walking or other activities. Greater duration of PA was associated with progressively less weight gain, but even an 11–20 minutes/day increase was beneficial; the benefits appeared stronger among those initially overweight. Sedentary behavior independently predicted weight gain.CONCLUSIONSSustained PA for at least 30 minutes/day, particularly if more intense, is associated with a reduction in long-term weight gain, and greater duration is associated with less weight gain. Sedentary women of any baseline weight who increase their PA will benefit, but overweight women appear to benefit the most.