This study investigated whether the addition of the high-intensity sweetener aspartame to a multidisciplinary weight-control program would improve weight loss and long-term control of body weight. One hundred sixty-three obese women were randomly assigned to consume or to abstain from aspartame-sweetened foods and beverages during 16 wk of a 19-wk weight-reduction program (active weight loss), a 1-y maintenance program, and a 2-y follow-up period. Women in both treatment groups lost approximately 10% of initial body weight (10 kg) during active weight loss. Among women assigned to the aspartame-treatment group, aspartame intake was positively correlated with percentage weight loss during active weight loss (r = 0.32, P < 0.01). During maintenance and follow-up, participants in the aspartame group experienced a 2.6% (2.6 kg) and 4.6% (4.6 kg) regain of initial body weight after 71 and 175 wk, respectively, whereas those in the no-aspartame group gained an average of 5.4% (5.4 kg) and 9.4% (9.4 kg), respectively. The aspartame group lost significantly more weight overall (P = 0.028) and regained significantly less weight during maintenance and follow-up (P = 0.046) than did the no-aspartame group. Percentage weight losses at 71 and 175 wk were also positively correlated with exercise (r = 0.32, P < 0.001; and r = 0.34, P < 0.01, respectively) and self-reported eating control (r = 0.37, P < 0.001; and r = 0.33, P < 0.01, respectively). These data suggest that participation in a multidisciplinary weight-control program that includes aspartame may facilitate the long-term maintenance of reduced body weight.