The Ethnic Density hypothesis posits that living around others from similar ethnic backgrounds reduces the risk of adverse mental health outcomes such as depression. Contrary to this hypothesis, previous work has shown that Hispanic ethnic density is cross-sectionally associated with increased depressive symptom severity among patients hospitalized with an acute coronary syndrome (ACS; myocardial infarction or unstable angina pectoris). To date, no study has examined the prospective association of Hispanic ethnic density on long-term depressive symptom severity following an acute medical event. We prospectively assessed the impact of Hispanic ethnic density on depressive symptoms, 1-year following an ACS event, among Hispanic adult patients. We tested the non-linear association between ethnic density and depressive symptoms to account for inconsistent findings on the ethnic density hypothesis. At the time of an index ACS event (i.e., baseline, N = 326) and 1-year later (N = 252), Hispanic patients from the Prescription Usage, Lifestyle, and Stress Evaluation prospective cohort study completed the Beck Depression Inventory as a measure of depressive symptom severity. Hispanic ethnic density was defined by the percentage of Hispanic residents within each patient’s census tract using data extracted from the American Community Survey Census (2010–2013). Covariates included baseline demographic factors (age, gender, English fluency, education, nativity status), cardiovascular factors (Charlson comorbidity index, left ventricular ejection fraction, Global Registry of Acute Coronary Events 6-month prognostic risk score), and neighborhood factors (residential density, income, and percentage of households receiving public assistance). In an adjusted multivariable linear regression analysis there was a significant curvilinear association between Hispanic ethnic density and depressive symptom severity at 1 year. As Hispanic ethnic density increased from low to moderate density, there was an increase in depressive symptoms, but depressive symptoms slightly declined in census tracts with the highest density of Hispanics. Furthermore, gender significantly moderated the relation between Hispanic ethnic density and 1-year depressive symptom severity, such that Hispanic ethnic density was significantly associated with increased depressive symptom severity for female Hispanic patients with ACS, but not for male Hispanic patients. Previous research suggests that ethnic density may be protective against depression in Hispanic enclaves; however, our findings suggest a non-linear ethnic density effect and an overall more complex association between ethnic density and depression. These data add to a growing body of literature on the effects of sociodemographic and contextual factors on health.