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Background: Inadequate self-management behaviors (e.g., not taking medications as prescribed) result in poor patient outcomes. eHealth literacy—the digital skills needed to seek and use health information from electronic sources—is critical for interacting with digital health technologies in a meaningful way to effectively manage chronic disease. Yet little is known about how eHealth literacy impacts self-management of chronic disease (e.g., heart disease), especially in minority populations. Methods: Using a cross-sectional observational design and convenience sampling, we enrolled 1259 English-speaking hospitalized patients ≥18 years of age at University of Chicago Medicine. Self-management was measured by a single question: "How well do you manage your illness at home (e.g., adhere to medication, keep track of symptoms)?” Participants responded on a five-point scale ranging from “not at all” (1) to “completely well” (5) (adequate self-management: ≥4; inadequate self-management: <3). eHealth literacy was measured with a validated eight-item questionnaire (composite score: 8–40; low literacy: <24; adequate literacy: ≥24). Associations between eHealth literacy and self-management adequacy were assessed using chi-square tests and logistic regression models, adjusting for age, gender, race, income, and education. Results: The sample was on average 54 (± 17.3) years old and mostly Black (73%), female (53%), and single/widowed/divorced (70%), and reported at least some college education (54%). 54% had hypertension, 29% had diabetes, 27% had heart disease; 54% were hospitalized in the last 12 months excluding current hospitalization. eHealth literacy showed a significant association with self-management adequacy (χ square = 8.2, p = 0.004; effect size = 0.225). Adequate eHealth literacy was linked to greater odds of reporting adequate self-management (OR = 3.62, 95% CI: 1.54–8.78, p = 0.003). After adjusting for covariates, the relationship was attenuated and non-significant (OR = 1.48, 95% CI: 0.34–6.74, p = 0.6), while higher age (OR = 1.06, 95% CI: 1.02–1.12, p = 0.009) and female gender (OR = 3.71, 95% CI: 1.05–14.7, p = 0.048) were independently associated with greater self-management adequacy. Conclusion: Interventions to improve digital health skills may enhance patients' ability to effectively manage their chronic illness. Additionally, demographic factors should be considered when designing interventions to improve self-management of chronic disease.