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Transdiagnostic cognitive behaviour therapy (TD-CBT) aims to target the symptoms of multiple disorders whereas disorder-specific CBT (DS-CBT) targets the symptoms of principal disorders. This study compared the relative benefits of internet-delivered TD-CBT and DS-CBT when provided in clinician-guided (CG-CBT) and self-guided (SG-CBT) formats for people with a principal diagnosis of Panic Disorder (PD). Participants (n = 145) were randomly allocated to receive TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of PD (Cohen's d ≥ 0.71; avg. reduction ≥ 36%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen's d ≥ 0.71; avg. reduction ≥ 33%), generalised anxiety disorder (Cohen's d ≥ 0.91; avg. reduction ≥ 34%) and social anxiety disorder (Cohen's d ≥ 0.50; avg. reduction ≥ 15%) were found over the 24-month follow-up period. Highlighting their efficacy and acceptability, no marked and consistent differences were observed between TD-CBT and DS-CBT or CG-CBT and DS-CBT. [ABSTRACT FROM AUTHOR]