Stellate Ganglion Block (SGB) is a rapid-acting intervention that may directly target PTSD biology. Positive case-studies and preliminary results from the investigators' team suggest clinically robust and significant benefits for up to 6-months. Two randomized controlled trials, however, yielded conflicting results and had methodological limitations, making interpretation of results inconclusive. Neither trial evaluated durability beyond 8-weeks, safety, or biological mechanisms along with clinical outcomes. Veteran demand for SGB for PTSD is high, creating time-sensitive urgency for a more definitive study in VA. The investigators propose a 4-year, multi-site, two-phase, three-arm, (SGB-experimental condition, Sham-placebo control, Wait-List Control (WLC)-for time, expectancy and safety) parallel-group, triple-blind, prospective randomized controlled trial (RCT) of SGB for PTSD. The sample will include 360 treatment-seeking Veterans with chronic PTSD randomized 1:1:1 to the three arms using an adaptive randomization procedure. Phase I is a 12-week RCT with the primary aims of evaluating: a) within and between group differences in the change in PTSD symptom severity from pre- to 8-weeks post-intervention, b) durability of symptom reduction after SGB over 12 weeks, and c) safety (i.e., SGB will be as safe as Sham and WLC). Phase II is a 12-week open-label extension period where subjects in all groups are offered active SGB if eligible (PTSD scores \> inclusion criteria scores at both primary Phase I endpoint of 8-weeks and durability endpoint of 12-weeks). Phase II is important because it allows evaluation of "enhanced dosing" (second SGB for those in the SGB arm), it allows all subjects to receive active intervention if they want, which also provides a larger sample of SGBs for exploratory pooled analyses, and it allows for analyses of durability over a longer time period for those in remission after Phase I. Another secondary aim is to test the hypothesis that SGB will be more biologically active than Sham or WLC by showing greater pre- to post-intervention reduction in highly PTSD-relevant fear-potentiated startle. The investigators will also explore clinical and biological phenotypic predictors of an SGB response (i.e., significant reduction in CAPS-5 scores). This superiority study is designed to expect and detect statistically and clinically important 30% PTSD symptom reduction from baseline to 8-week endpoint for SGB,15% reduction for Sham and 5% reduction for WLC in a sample with moderately severe PTSD (baseline score of 65+18). With these assumptions the investigators require a sample size of 262 subjects to test the primary hypothesis of clinical efficacy. The investigators will sample 360 subjects to account for 10% attrition, 5% missing data, a 5% failed-block rate and will oversample due to site variability. It is critical to ensure adequate power for this time-sensitive study. General linear mixed models (repeated multivariate analysis of variance (MANOVA)) will be used to evaluate the primary clinical hypothesized effects of intervention (SGB) on the clinical outcome of PTSD symptom severity (CAPS-5) over time (pre- to post-treatment to follow-up), controlling for baseline severity of symptoms and demographic characteristics (e.g., age, gender) in comparison with placebo control group (Sham) and WLC group with assumption of intent to treat while simultaneously adjusting for any significant covariates. Cohen's d within and between subjects will be calculated. Analyses will be performed on missing data due to loss-to-follow-up in order to determine if any potential bias exists once missing data are withdrawn. Details for analyses of the three primary aims are in the data analysis section of the Research Plan. The leadership team has extensive clinical and research experience with clinical trials, the use and adaptation of SGB for PTSD, and a national initiative to provide SGB to PTSD patients on a compassionate care basis. The proposed definitive study will guide rational use of SGB for PTSD in VA, will stimulate further research about dose, timing, biological mechanisms and clinical predictors of outcome, and will have established VA sites poised for further SGB research and clinical practice.