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Emotional Freedom Technique (EFT) is an evidence-based self-help therapeutic method and over 100 studies demonstrate its efficacy. However, information about the physiological effects of EFT is limited. The current study sought to elucidate EFTs mechanisms of action across the central nervous system (CNS) by measuring heart rate variability (HRV) and heart coherence (HC); the circulatory system using resting heart rate (RHR) and blood pressure (BP); the endocrine system using cortisol, and the immune system using salivary immunoglobulin A (SigA). The second aim was to measure psychological symptoms. Participants (N = 203) were enrolled in a 4-day training workshop held in different locations. At one workshop (n = 31), participants also received comprehensive physiological testing. Posttest, significant declines were found in anxiety (−40%), depression (−35%), posttraumatic stress disorder (−32%), pain (−57%), and cravings (−74%), all P < .000. Happiness increased (+31%, P = .000) as did SigA (+113%, P = .017). Significant improvements were found in RHR (−8%, P = .001), cortisol (−37%, P < .000), systolic BP (−6%, P = .001), and diastolic BP (−8%, P < .000). Positive trends were observed for HRV and HC and gains were maintained on follow-up, indicating EFT results in positive health effects as well as increased mental well-being.