Abstract: Posttraumatic Stress Disorder (PTSD) is a debilitating disorder characterized by re-experiencing aspects of the original trauma, avoidance of trauma reminders, negative alterations in cognition and mood, and hyperarousal. Current evidence-based treatments for PTSD have both value and limitations, most notably slow response and high withdrawal rates. The field is searching for more rapid and highly effective interventions. The Stellate Ganglion Block (SGB), which has historically been used to treat regional pain syndromes, causalgia (nerve injury), and intractable angina, has support for being a rapid and highly effective intervention from multiple case series. However, one of two published RCTs was negative and the other had limitations. A larger more definitive study is necessary to provide the evidence needed to determine if SGB is an effective intervention. This paper describes the background, theory and methods of a multi-site triple-blind placebo-controlled trial about the efficacy and safety of the SGB for PTSD. Elements that make this a more definitive study include using and describing a reliably conducted sham, using a standard dose of anesthetic, including an untreated group, rigorously assessing side-effects and safety, and evaluating durability, enhanced dosing, and an objective physiological outcome measure (fear-potentiated startle) to evaluate treatment response in addition to the clinical effect. The strengths and limitations of this research are also presented. Clinical trial registration: This study is registered on ClinicalTrials.gov ID NCT05169190