Objective: This study, to the authors' knowledge, is the first randomized controlled trial comparing the efficacy of cognitive behavior therapy (CBT), paroxetine, and a placebo (administered in a double blind fashion) in the treatment of hypochondriasis. Method: The authors randomly assigned 112 subjects with hypochondriasis according to DSM-IV criteria to 16 weeks of outpatient treatment with CBT, paroxetine, or a placebo. The main outcome measure was the Whiteley Index. The authors made pretest and posttest assessments and analyzed all outcome measures using a General Linear Model 3"2 repeated measures analysis of variance with Helmert contrasts. The authors considered subjects who scored at least one standard deviation below the mean pretest score on the Whiteley Index as responders. All analyses were conducted on intent-to-treat and completer bases. Results: On the Whiteley Index, Helmert contrasts on the intent-to-treat and completer cohorts revealed that pooled CBT and paroxetine were significantly superior to placebo, but did not differ significantly from each other. The responder analysis on the intent-to-treat cohort and completer cohort, respectively, revealed the following percentages of responders per group: CBT group, 45% and 54%; paroxetine group, 30% and 38%; and placebo group, 14% and 12%. In the intent-to-treat analysis, only CBT differed significantly from the placebo. In the completer analysis, both paroxetine and CBT differed significantly from the placebo. Conclusions: CBT or paroxetine are effective short-term treatment options for subjects with hypochondriasis.