Background: Acute bleeding from esophageal varices is repeatedly a remarkable event. The main goal of care is minimizing complications that affected by patient compliance to therapeutic regimen. Aim of the study: Was to assess factors affecting esophageal varices patients' compliance to therapeutic regimen and suggested guidelines. Research design: A descriptive design utilized to carry out this study. Sample: A convenient sample of 100 esophageal varices patients in GIT endoscopy unit and internal medicine units at Benha University Hospital over a period of six months. Tools for data collection: I) Interview schedule which include a) Socio demographic data sheet, b) Knowledge assessment sheet. II) Compliance assessment sheet to assess compliance of patients with esophageal varices to therapeutic regimen. III) Non-Compliance assessment sheet to assess factors affecting compliance of patients to therapeutic regimen. Results: revealed that majority of patients (68%) of patients had unsatisfactory knowledge about disease and its therapeutic management. As well as, (61%) of them had low level of compliance to therapeutic regimen. The most common factors affecting patients' compliance were, dyspnea(94%), socio-economic factors(96%) and uncooperative family(59%) as well as having insomnia an feeling of worry(100%). There was a significant statistical relation between compliance of the study group and their education, income and smoking. Conclusion and Recommendations: In addition to non-compliance factors; the current study concluded that patients' compliance is affected by physical illness, socio-economic factors and psychological factors. Patients benefited from the given suggested guidelines, but further research is needed for developing interventions to improve compliance of EV patients.