Background: Preventing hospitalization and improving event-free survival are primary goals of heart failure (HF) treatment according to current European Society of Cardiology guidelines; however, substantial uncertainty remains in our ability to predict risk and improve outcomes. Although caregivers often assist patients to manage their HF, little is known about their influence on clinical outcomes. Aims: To quantify the influence of patient and caregiver characteristics on patient clinical event risk in HF. Methods: This was a secondary analysis of data using a sample of Italian adults with HF and their informal caregivers (n = 183 patient–caregiver dyads). HF patients were followed over 12 months for the following clinical events: hospitalization for HF, emergency room visit for HF or all-cause mortality. Influence of baseline caregiver- and patient-level factors (patient and caregiver age; dyad relationship type; patient New York Heart Association (NYHA) Class, cognition, and comorbidities; and caregiver strain, mental health status, and contributions to HF self-care) on patient risk of death or hospitalization/emergency room use was quantified using Cox proportional hazards regression. Results: Over the course of follow up, 32.8% of patients died, 19.7% were hospitalized for HF and 10.4% visited the emergency room. Higher caregiver strain, better caregiver mental health status and greater caregiver contributions to HF self-care maintenance were associated with significantly better event-free survival. Worse patient functional class and greater caregiver contributions to patient self-care management were associated with significantly worse patient event-free survival. Conclusion: Considering caregiving factors together with patient factors significantly increases our understanding of patient clinical event risk in HF.