Anxiety sensitivity (AS) is a common vulnerability in emotional disorders. Due to the pathological role of AS, individuals with high AS are faced with emotional problems. Thus, cognitive behavioural interventions try to reduce these problems by targeting AS. The present study aimed to compare the efficacy of transdiagnostic cognitive behavioural therapy (T-CBT) and construct-specific CBT (CS-CBT) on AS, anxiety, depression, and positive and negative affect in these patients. To this end, 40 patients with high AS were randomly assigned to one of the three groups of T-CBT, CS-CBT, and wait list. Participants were assessed using the Anxiety and Related Disorders Interview Schedule for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Anxiety Sensitivity Index-3, Beck Anxiety Inventory, Beck Depression Inventory-II, and Positive and Negative Affect Schedule at baseline, post-treatment, 3-month follow-up, and 6-month follow-up. The findings showed that T-CBT and CS-CBT have a significant effect on AS, anxiety, and negative affect; however, contrary to T-CBT, CS-CBT is not effective for reducing depression and positive affect. T-CBT had a more promising efficacy than CS-CBT in all treatment outcomes. The results show better and more stable efficacy of T-CBT among patients with high AS. It is essential to consider AS as a target for cognitive behavioural intervention for the spectrum of emotional disorders.