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Background: Health anxiety is common, disabling and costly due to patients' extensive use of health care services. Internet-delivered treatment may overcome barriers of accessibility to specialized treatment. We aimed to evaluate the efficacy of internet-delivered acceptance and commitment therapy (iACT). Methods: A randomized, controlled trial of iACT versus an internet-delivered discussion forum (iFORUM), performed in a Danish university hospital setting. Patients self-referred and underwent video-diagnostic assessment. Eligible patients (≥18 years) with health anxiety were randomized to 12 weeks of intervention. The randomization was blinded for the assessor. The primary outcome was between-group unadjusted mean differences in health anxiety symptoms measured by the Whiteley-7 Index (WI-7, range 0–100) from baseline to 6-month follow-up (6-MFU) using intention to treat and a linear mixed model. The study is registered at clinicaltrials.gov, number NCT02735434. Results: A total of 151 patients self-referred, and 101 patients were randomized to iACT (n = 53) or iFORUM (n = 48). A mean difference in change over time of 19.0 points [95% confidence interval (CI) 10.8–27.2, p < 0.001] was shown on the WI-7, and a large standardized effect size of d = 0.80 (95% CI 0.38–1.23) at 6-MFU. The number needed to treat was 2.8 (95% CI 1.8–6.1, p < 0.001), and twice as many patients in iACT were no longer clinical cases (35% v. 16%; risk ratio 2.17, 95% CI 1.00–4.70, p = 0.050). Adverse events were few and insignificant. Conclusions: iACT for health anxiety led to sustained effects at 6-MFU. The study contributes to the development of easily accessible treatment options and deserves wider application. [ABSTRACT FROM AUTHOR]