Despite the acknowledged favorable side effects profile of selective serotonin reuptake inhibitors (SSRIs), comparative studies have not found significant differences in efficacy between tricyclics (TCAs) such as imipramine and clomipramine, and SSRIs in the treatment of panic disorder. The present study focuses on treatment completers to inform patients who adhere to a recommended course of treatment on the possible differential patterns of improvement and of change in side effects between sertraline and imipramine. From an intent to treat consecutive sample of patients participating in the 24-week open phase protocolized treatment of a long-term controlled maintenance/discontinuation study, 20 imipramine completers and 16 sertraline completers with moderate to severe baseline symptomatology were compared using primarily repeated measures analysis of variance on measures of symptom severity, on 15 side effects systematically elicited using an inventory and on heart rate and weight. The results revealed greater early improvement with imipramine compared to sertraline but no enduring differences beyond week 8 of treatments. Side effects, in particular dry mouth, constipation, tremors, sweating, and cardiovascular complaints increased more in severity and were more frequent and persistent during imipramine than sertraline but, except for the 10 beats/min increase in heart rate, side effects were clinically insignificant at the end of both treatments. Change in sexual complaints and weight did not differ between the treatments. The more favorable side effect profile of SSRIs versus TCAs was demonstrated even in the best case scenario of treatment completers. The more rapid improvement with imipramine needs replication but, tentatively, it may be attributed to the greater motivational effects toward action observed with noradrenergic or dual action antidepressants compared to SSRIs.