BACKGROUND: Little is known regarding the prevalence or risk factors for non-comprehension and noncompliance with discharge instructions among older adults. OBJECTIVE: To quantify the prevalence of noncomprehension and non-compliance with discharge instructions and to identify associated patient characteristics. RESEARCH DESIGN: Prospective cohort study. SUBJECTS: Four hundred and fifty adults aged ≥ 65 admitted to medical and surgical units of a tertiary care facility and meeting inclusion criteria. MEASURES: We collected information on demographics, psycho-social factors, discharge diagnoses, and medications using surveys and patient medical records. Domains within discharge instructions included medications, follow-up appointments, diet, and exercise. At 5 days post-discharge, we assessed comprehension by asking patients about their discharge instructions, and compared responses to written instructions from medical charts. We assessed compliance among patients who understood their instructions. RESULTS: Prevalence of non-comprehension was 5 % for follow-up appointments, 27 % for medications, 48 % for exercise and 50 % for diet recommendations. Age was associated with non-comprehension of medication [odds ratio (OR) 1.07; 95 % confidence interval (CI) 1.04, 1.12] and follow-up appointment (OR 1.08; 95 % CI 1.00, 1.17) instructions. Male sex was associated with noncomprehension of diet instructions (OR 1.91; 95 % CI 1.10, 3.31). Social isolation was associated with noncomprehension of exercise instructions (OR 9.42; 95 % CI 1.50, 59.11) Depression was associated with noncompliance with medication (OR 2.29; 95 % CI 1.02, 5.10) and diet instructions (OR 3.30; 95 % CI 1.24, 8.83). CONCLUSIONS: Non-comprehension of discharge instructions among older adults is prevalent, multifactorial, and varies by domain.