The current open trial evaluated an inference‐based approach (IBA) to the treatment of obsessive–compulsive disorder (OCD) across symptom subtypes and treatment‐resistant cases. Following formal diagnosis through semi‐structured interview by an independent evaluator, a total of 125 OCD participants across five major symptom subtypes entered a program of 24 sessions of treatment based on the IBA. An additional group of 22 participants acted as a natural wait‐list control group. Participants were administered the Yale–Brown Obsessive–Compulsive Scale before and after treatment as the principal outcome measure, as well as measures of negative mood states, inferential confusion and obsessive beliefs. Level of overvalued ideation was assessed clinically at pre‐treatment using the Overvalued Ideation Scale. After 24 weeks of treatment, 102 treatment completers across all major subtypes of OCD showed significant reductions on the Yale–Brown Obsessive–Compulsive Scale with effect sizes ranging from 1.49 to 2.53 with a clinically significant improvement in 59.8% of participants. No improvement was observed in a natural wait‐list comparison group. In addition, IBA was effective for those with high levels of overvalued ideation. Change in inferential confusion and beliefs about threat and responsibility were uniquely associated with treatment outcome. The study is the first large‐scale open trial showing IBA to be effective across symptom subtypes and treatment‐resistant cases. The treatment may be particularly valuable for those who have previously shown an attenuated response to other treatments. Copyright © 2016 John Wiley & Sons, Ltd. Key Practitioner Message Psychological treatment based on the inference‐based approach is an effective treatment for all major subtypes of obsessive–compulsive disorder. The treatment is equally effective for those with high and low levels of overvalued ideation. Treatment based on the inference‐based approach may be particularly valuable for those who have shown an attenuated response to cognitive–behaviour therapy as usual.