Endoscopic variceal ligation (EVL) and nonselective beta-blockers (hereafter just called beta-blockers) are both effective for primary prophylaxis for variceal hemorrhage; however, the route of administration and side effects of these treatments are distinct. The objective of this study was to examine predicted preferences of patients and physicians for the primary prevention of variceal hemorrhage. Untreated patients with newly diagnosed esophageal varices and practicing gastroenterologists were enrolled in this study. Patients with contraindications to either EVL or beta-blockers were excluded. Predicted preferences for treatment were evaluated with an interactive computer task designed to elicit subjects' trade-offs related to the route of administration, risk of fatigue, sexual dysfunction, dysphagia, shortness of breath and/or hypotension, procedure-related bleeding, and perforation. Fifty-three patients and 61 physicians were enrolled. Thirty-four (64%) patients and 35 (57%) physicians preferred EVL over beta-blockers. Patients' predicted preferences were most strongly influenced by the risks of shortness of breath or hypotension, fatigue, and procedure-related bleeding, whereas physicians placed greater importance on procedure-related bleeding, sexual dysfunction, and perforation. Forty-eight patients were prescribed beta-blockers, two were not given prophylaxis, and three were lost to follow-up. Conclusion: Predicted treatment preferences among both patients and physicians for primary prophylaxis of variceal hemorrhage vary significantly. Physicians in this study preferring EVL stated that they prescribe beta-blockers as first-line therapy in order to remain compliant with guidelines. Physicians should discuss both EVL and beta-blockers with patients requiring primary prophylaxis for variceal hemorrhage. Future guidelines should incorporate individual patient preferences. (HEPATOLOGY 2008;47:169-176.) S creening for esophageal varices and the use of prophylactic therapies to prevent a first variceal hemorrhage is an essential component of care for patients with cirrhosis. 1 Two treatment options have been proven to be effective in preventing first variceal bleeding in patients with cirrhosis and large varices: nonselective beta-blockers (hereafter just called beta-blockers) and endoscopic variceal ligation (EVL). 1,2 Meta-analyses show that, compared with no treatment or a placebo, betablockers reduce the risk of first variceal hemorrhage from approximately 30% to 14% over two years in patients with medium/large varices 3 and improve survival. 4 Two recent meta-analyses of studies comparing beta-blockers and EVL show that EVL is marginally more effective than beta-blockers in preventing first variceal hemorrhage without any differences in mortality. 5,6 Expert consensus recommends beta-blockers as first-line therapy and EVL for those with contraindications or intolerance to betablockers. 7 The principles of patient autonomy and informed consent prescribe that patients should be informed of all available treatment options and that their preferences should be incorporated into treatment decisions made in