Many of the soldiers returning home from Operation Enduring Freedom and Operation Iraqi Freedom with PTSD will require multiple surgical procedures in order to treat their physical injuries. Although PTSD is a psychiatric diagnosis, there is epidemiological data linking the diagnosis of PTSD with co-morbid medical conditions and lifestyle behaviors that are major risks factors for perioperative morbidity and mortality.I.3 We recently confirmed this link in a surgical patient population, and found that the diagnosis of PTSD at the time of surgery in patients who are undergoing elective surgery requiring admission was associated with I) significantly increased prevalence of cardiac risk factors 2) significantly increased prevalence of delirium and renal failure in the postoperative period, and 3) significantly increased 1- and 5-year postoperative mortality. In addition, PTSD diagnosis in the age group 55-70 years of age, undergoing thoracic, vascular, and orthopedic surgery requiring admission was associated with a significantly increased hospital length of stay (LOS). Our findings indicate that patients with PTSD are at high risk for both cardiovascular and central nervous system morbidity, with the established elevated central nervous system norepinephrine concentrations in PTSD4,5 being the most likely underlying mechanism. Central blockade of adrenergic system with alpha-2 receptor agonists and peripheral blockade with beta blockers have an established track record of beneficial effects on mortality.6.10 In addition, the central adrenergic blockade with alpha-2 agonists was found to reduce the incidence of delirium in ICU. 11 ,12 Since PTSD is associated with symptoms related to peripheral as well as central adrenergic receptors that are amenable to treatment, this proposal will examine if perioperative blockade ofthe central and peripheral beta-adrenergic system with propranolol is an effective treatment to improve the perioperative medical and psychiatric morbidity and mortality.