OBJECTIVE: To establish whether the combination of cognitive-behavioral therapy (CBT) and pharmacotherapy (SSRI) was more effective in treating panic disorder (PD) than either CBT or SSRI alone, and to evaluate any differential effects between the mono-treatments. METHOD: Patients with PD (n = 150) with or without agoraphobia received CBT, SSRI or CBT + SSRI. Outcome was assessed after 9 months, before medication taper. RESULTS: CBT + SSRI was clearly superior to CBT in both completer and intent-to-treat analysis (ITT). Completer analysis revealed superiority of CBT + SSRI over SSRI on three measures and no differences between CBT and SSRI. ITT analysis revealed superiority of SSRI over CBT on four measures and no differences between CBT + SSRI and SSRI. CONCLUSION: Both the mono-treatments (CBT and SSRI) and the combined treatment (CBT + SSRI) proved to be effective treatments for PD. At post-test, CBT + SSRI was clearly superior to CBT, but differences between CBT + SSRI and SSRI, and between SSRI and CBT, were small.