CONTEXT: Behavioral weight loss interventions achieve short-term success, but re-gain is common. OBJECTIVE: To compare 2 weight loss maintenance interventions with a self-directed control group. DESIGN, SETTING, AND PARTICIPANTS: Two-phase trial in which 1032 overweight or obese adults (38% African American, 63% women) with hypertension, dyslipidemia, or both who had lost at least 4 kg during a 6-month weight loss program (phase 1) were randomized to a weight-loss maintenance intervention (phase 2). Enrollment at 4 academic centers occurred August 2003-July 2004 and randomization, February-December 2004. Data collection was completed in June 2007. INTERVENTIONS: After the phase 1 weight-loss program, participants were randomized to one of the following groups for 30 months: monthly personal contact, unlimited access to an interactive technology–based intervention, or self-directed control. MAIN OUTCOME: Changes in weight from randomization. RESULTS: Mean entry weight was 96.7 kg. During the initial 6-month program, mean weight loss was 8.5 kg. After randomization, weight regain occurred. Participants in the personal-contact group regained less weight (4.0 kg) than those in the self-directed group (5.5 kg; mean difference at 30 months, −1.5 kg; 95% confidence interval [CI], −2.4 to −0.6 kg; P = .001). At 30 months, weight regain did not differ between the interactive technology–based (5.2 kg) and self-directed groups (5.5 kg; mean difference −0.3 kg; 95% CI, −1.2 to 0.6 kg; P = .51); however, weight regain was lower in the interactive technology–based than in the self-directed group at 18 months (mean difference, −1.1 kg; 95% CI, −1.9 to −0.4 kg; P = .003) and at 24 months (mean difference, −0.9 kg; 95% CI, −1.7 to −0.02 kg; P = .04). At 30 months, the difference between the personal-contact and interactive technology–based group was −1.2 kg (95% CI −2.1 to −0.3; P = .008). Effects did not differ significantly by sex, race, age, and body mass index subgroups. Overall, 71% of study participants remained below entry weight. CONCLUSIONS: The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level. Monthly brief personal contact provided modest benefit in sustaining weight loss, whereas an interactive techonology–based intervention provided early but transient benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00054925