Hypertension remains a leading global cause of cardiovascular morbidity and mortality, with sub-Saharan Africa experiencing disproportionately high rates despite the availability of diverse antihypertensive therapies. Effective management of hypertension requires not only appropriate diagnosis and therapy selection but also adherence to evidence-based prescribing guidelines. This study evaluates the prescribing patterns of antihypertensive medications and the extent to which these practices align with the Eighth Report of the Joint National Committee (JNC-8) guidelines in a tertiary hospital in Southern Nigeria. Prescribing patterns provide critical insight into clinical decision-making, enabling the identification of areas requiring improvement for optimal, rational, and cost-effective patient care. Medication prescriptions are determined following careful patient assessment, with clinicians selecting therapeutic regimens tailored to individual health needs. Writing effective prescriptions demands expertise, knowledge of pharmacology, and understanding of clinical guidelines. The JNC-8 guidelines, the most recent comprehensive framework for hypertension management, provide evidence-based recommendations regarding therapy thresholds, treatment goals, and drug selection, including specific advantages of monotherapy or combination therapy for different patient populations. By comparing real-world prescribing patterns to these guidelines, this study identifies gaps in compliance, informs clinical practice improvements, and underscores the importance of guideline-directed therapy in reducing hypertension-related complications. The findings emphasize the need for continued education of prescribers, regular review of prescription practices, and adherence to updated hypertension guidelines to ensure optimal patient outcomes. Enhancing compliance with JNC-8 recommendations is critical for improving therapeutic efficacy, minimizing adverse effects, and reducing the burden of cardiovascular disease in Nigerian populations.