Objective: There have been few comparisons of the effectiveness of collaborative depression care between older versus younger adults with comorbid illness, particularly among low-income populations. Design: Intent-to-treat analyses are conducted on pooled data from three randomized controlled trials that tested collaborative care aimed at improving depression, quality of life, and treatment receipt. Settings: Trials were conducted in oncology and primary care safety net clinics and diverse home healthcare programs. Participants: Thousand eighty-one patients with major depressive symptoms and cancer, diabetes, or other comorbid illness. Intervention: Similar intervention protocols included patient, provider, sociocultural, and organizational adaptations. Measurements: The Patient Health Questionnaire (PHQ)-9 depression, Short-Form Health Survey-12/20 quality of life, self-reported hospitalization, ER, intensive care unit utilization, and antidepressant, psychotherapy treatment receipt are assessed at baseline, 6, and 12 months. Results: There are no significant differences in reducing depression symptoms (p ranged 0.18-0.58), improving quality of life (t = 1.86, df = 669, p = 0.07 for physical functioning at 12 months, and p ranged 0.23-0.99 for all others) patients aged between >= 60 years versus 18-59 years. Both age group intervention patients have significantly higher rates of a 50% PHQ-9 reduction (older: Wald chi(2)[df = 1] = 4.82, p = 0.03; younger: Wald chi(2)[df = 1] = 6.47, p = 0.02), greater reduction in major depression rates (older: Wald chi(2)[df = 1] = 7.72, p = 0.01; younger: Wald chi(2)[df = 1] = 4.0, p = 0.05) than enhanced-usual-care patients at 6 months and no significant age group differences in treatment type or intensity. Conclusion: Collaborative depression care in individuals with comorbid illness is as effective in reducing depression in older patients as younger patients, including among low-income, minority patients. Patient, provider, and organizational adaptations of depression care management models may contribute to positive outcomes. (Am J Geriatr Psychiatry 2010; 18:520-530)