OBJECTIVE This study assessed the impact of an Internet-delivered care management and patient self-management program, eCare for Moods, on patients treated for recurrent or chronic depression. METHODS Patients with recurrent or chronic depression were randomly assigned to eCare (N=51) or usual specialty mental health care (N=52). The 12-month eCare program integrates with ongoing depression care, links to patients' electronic medical records, and provides clinicians with panel management and decision support. Participants were interviewed at baseline and six, 12, 18, and 24 months after enrollment. Telephone interviewers blind to treatment used a timeline follow-back method to estimate depression severity on a 6-point scale for each of the 105 study weeks (including the baseline). Differences between groups in weekly severity over two years were examined by generalized estimating equations. RESULTS Participants in eCare experienced more reduction in depressive symptoms (estimate=-.74 on the 6-point scale over two years; 95% confidence interval [CI]=-1.38 to -.09, p=.025) and were less often depressed (-.24 over two years; CI=-.46 to -.03, p=.026). At 24 months, 43% of eCare and 30% of usual-care participants were depression free; the number needed to treat to attain one additional depression-free participant was 8. eCare participants had other favorable outcomes: improved general mental health (p=.002), greater satisfaction with specialty care (p=.003) and with learning new coping skills (p<.001), and more confidence in managing depression (p=.006). CONCLUSIONS Internet-delivered care management can help improve outcomes of patients treated for recurrent or chronic depression.