Objective: The present study is based on a previously reported successful randomized controlled trial (RCT) on Acceptance and Commitment Group therapy (ACT-G) for severe health anxiety (HA) and investigates intervening variables of ACT for HA. The process primarily targeted by ACT is psychological flexibility (PF). No randomized study has yet examined the possible intervening variables of ACT for HA. Methods: 126 patients diagnosed with severe HA were enrolled in the RCT of which 107 were included in the analyses. The outcome measure was illness worry (Whiteley Index) and included process variables were PF and facets of mindfulness. Results: Statistically significant indirect effects (IE) of ACT-G on the outcome of illness worry 6 months after treatment were found for PF (IE = -5.5, BCa 99% CI -123;-1.2) and one mindfulness subscale, namely ton-react' (IE = -6.5 BCa 99% CI -15.3: 1.0). Conclusion: In line with the ACT model of change, PF may have a small to moderate IE on decrease in illness worry. Of the mindfulness scales, only 'non-react' showed a significant IE. Although tentative, due to no active comparison control condition, these results support that PF is a intervening variable in ACT treatment aimed at reducing illness worry in patients with severe HA. (C) 2017 Elsevier Ltd. All rights reserved.