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Background: There is a need for improved understanding of why 20–30% of individuals with anorexia nervosa (AN) develop a severe and enduring form of illness (SE-AN). Previously, we reported differences in proactive inhibition (a pre-emptive slowing of responses) in individuals with AN compared to healthy controls (after controlling for intolerance of uncertainty). The present study is a preliminary exploration of proactive inhibition in which we compared women with SE-AN with healthy comparison (HC) women and explored its association with restrictive/avoidant eating behaviours. Methods: Thirty-four women with SE-AN (defined by >3 years of illness and a previous unsuccessful course of eating disorder treatment) and 30 HCs completed (a) a cued reaction time task, to assess proactive inhibition, and (b) questionnaires assessing restrictive/avoidant eating behaviours and intolerance of uncertainty. Results: Both SE-AN and HC participants showed slower reaction times under conditions of uncertainty, indicating proactive inhibition in both groups. There was a main effect of group, with SE-AN participants showing significantly slower reaction times compared to HC. There was no interaction between group and condition, suggesting that individuals with SE-AN did not differ in proactive inhibition compared to HCs. However, post-hoc analysis between-group tests for each trial type revealed that group differences were only present under conditions of uncertainty. Proactive inhibition was not significantly associated with self-reported restrictive/avoidant eating behaviours, including when taking intolerance of uncertainty into consideration. Conclusions: It is unlikely that proactive inhibition contributes to avoidant and restrictive eating behaviours seen in SE-AN. Our findings suggest that the SE-AN group are relatively more cautious when responding under conditions of uncertainty. Longitudinal studies and between-group comparisons of individuals across different stages of illness will be required to elucidate the way in which proactive inhibition is specifically implicated in SE-AN, rather than in AN more generally. Plain English Summary: Proactive inhibition refers to the pre-emptive slowing of responses. We assessed whether 34 women with severe and enduring anorexia nervosa (defined by greater than 3 years of illness and a previous unsuccessful course of treatment) differed from 30 healthy comparison women in proactive inhibition. We also explored if proactive inhibition was related to restrictive eating behaviours. All participants completed a cued reaction time task to assess proactive inhibition and questionnaires assessing restrictive/avoidant eating behaviours and intolerance of uncertainty. All participants showed proactive inhibition, i.e., slower reaction times under conditions of uncertainty. Participants with severe and enduring anorexia nervosa showed significantly slower reaction times compared to healthy comparison women. Proactive inhibition was not significantly associated with self-reported restrictive/avoidant eating behaviours. Our findings suggest that compared to the healthy comparison group of women, the severe and enduring anorexia nervosa group are more cautious when responding, specifically in the context of uncertainty. It is unlikely that proactive inhibition contributes to avoidant and restrictive eating behaviours in severe and enduring anorexia nervosa. [ABSTRACT FROM AUTHOR]