To consider autonomic status as a predictor of anti-tumor necrosis factor (TNF) treatment response for inflammatory arthritis, we conducted an exploratory, double-blind, 52-week study with 33 patients with rheumatoid (25) or psoriatic (8) arthritis using heart rate variability (HRV). All were assessed for parasympathetic, sympathetic, total power and tension index measures of autonomic reactivity at initiation of anti-TNF therapy with etanercept (15) or adalimumab (18). Clinical response was assessed at 6, 12, 26 and 52 weeks by internationally accepted outcome criteria (ACR20/50/70 and DAS28 response). Predictive value was demonstrated for all HRV assessments (p-value range 0.001-0.032), except sympathetic (p-value range 0.06-0.22), for ACR20, ACR50 and ACR70 at 52 weeks and at as early as 6 weeks for some measures. Only parasympathetic and tension index predicted DAS28 outcome (p-value range 0.009-0.024). Poor anti-TNF response was associated with low parasympathetic, low total power, high sympathetic and high tension index measures, a profile also predominant in the prior anti-TNF failure subset (12). In conclusion, this unique, exploratory study suggests that HRV may be a novel, useful predictor of response to anti-TNF therapy in patients with inflammatory arthritis, and emphasizes the importance of autonomic influence of autoimmune disease expression.