Objective: The authors assessed whether adding cognitive behavior therapy (CBT) to imipramine for patients with panic disorder decreased the severity of side effects and dropouts from side effects. Method: Data were analyzed for 172 panic disorder patients who were randomly assigned to receive imipramine alone, imipramine plus CBT, or placebo. Mixed-effects models were used to assess longitudinal differences among the treatment groups with respect to side effect burden and dropout rates during the acute, maintenance, and follow-up phases of treatment. Results: Patients treated with imipramine plus CBT experienced less severe fatigue/weakness, dry mouth, and sweating and had a lower rate of dropout due to side effects compared with those treated with imipramine only. Conclusions: The addition of CBT to medication treatment with imipramine was associated with less severe side effects and fewer dropouts due to perceived side effects than treatment with imipramine alone.