BACKGROUND: Evidence-based interventions to reduce hospital readmissions may not generalize to resourceconstrained safety-net hospitals. OBJECTIVE: To determine if an intervention by patient navigators (PNs), hospital-based Community Health Workers, reduces readmissions among high risk, low socioeconomic status patients. DESIGN: Randomized controlled trial. PARTICIPANTS: General medicine inpatients having at least one of the following readmission risk factors: (1) age≥60 years, (2) any in-network inpatient admission within the past 6 months, (3) length of stay≥3 days, (4) admission diagnosis of heart failure, or (5) chronic obstructive pulmonary disease. The analytic sample included 585 intervention patients and 925 controls. INTERVENTIONS: PNs provided coaching and assistance in navigating the transition from hospital to home through hospital visits and weekly telephone outreach, supporting patients for 30 days post-discharge with discharge preparation, medication management, scheduling of follow-up appointments, communication with primary care, and symptom management. MAIN MEASURES: The primary outcome was in-network 30-day hospital readmissions. Secondary outcomes included rates of outpatient follow-up. We evaluated outcomes for the entire cohort and stratified by patient age >60 years (425 intervention/584 controls) and ≤60 years (160 intervention/341 controls). KEY RESULTS: Overall, 30-day readmission rates did not differ between intervention and control patients. However, the two age groups demonstrated marked differences. Intervention patients >60 years showed a statistically significant adjusted absolute 4.1 % decrease [95 % CI: −8.0 %, -0.2 %] in readmission with an increase in 30-day outpatient follow-up. Intervention patients ≤60 years showed a statistically significant adjusted absolute 11.8 % increase [95 % CI: 4.4 %, 19.0 %] in readmission with no change in 30-day outpatient follow-up. CONCLUSIONS: A patient navigator intervention among high risk, safety-net patients decreased readmission among older patients while increasing readmissions among younger patients. Care transition strategies should be evaluated among diverse populations, and younger high risk patients may require novel strategies.KEY WORDS: care transitions; continuity of care; health care delivery; patient safety; underserved populations. J Gen Intern Med 30(7):907-15