Background: Medication non-adherence remains a major challenge among patients with heart failure (HF) and is associated with adverse clinical outcomes, including increased hospitalization and mortality. Prescription discrepancies may further contribute to poor adherence and unfavorable outcomes. This study aimed to assess the prevalence of medication non-adherence and prescription discrepancies, identify associated factors, and evaluate their relationship with HF-related rehospitalization. Methods: This prospective observational study included adult patients with HF attending an ambulatory HF clinic between July 2023 and April 2024. The primary outcomes were the proportion of patients demonstrating medication adherence and the prevalence, number, and types of prescription discrepancies. Secondary outcomes included assessment of health literacy, identification of factors associated with medication non-adherence, and evaluation of HF-related rehospitalization and its association with medication non-adherence, prescription discrepancies, and health literacy. Results: A total of 202 patients were included. The mean age was 60.4 ± 14.1 years, and 69.3% were male. High medication adherence was observed in 43.6% of patients, while 39.6% and 16.8% demonstrated medium and low adherence, respectively. Prescription discrepancies were identified in 104 patients (51.5%), resulting in 178 discrepancy events, most of which were patient-generated (70.2%). Marginal and inadequate health literacy were identified in 51.5% and 24.8% of patients, respectively. Polypharmacy, limited health literacy, younger age, and adverse medication effects were significantly associated with medication non-adherence. During the six-month follow-up, 18 patients (8.9%) experienced HF-related rehospitalization. Medium/low medication adherence, prescription discrepancies, and limited health literacy were independently associated with rehospitalization in multivariable logistic regression analysis. Conclusions: Medication non-adherence and prescription discrepancies were highly prevalent among HF patients in the ambulatory care setting and were significantly associated with HF-related rehospitalization. Limited health literacy and polypharmacy represented major contributors to non-adherence. These findings underscore the need for multidisciplinary interventions, medication reconciliation, and patient-centered educational strategies to improve medication management and clinical outcomes in HF patients.