Researchers evaluated the effectiveness of cognitive behavioral therapy programs in outpatients Background Among some patients referred to psychology services, treatment specialists found particular advantages in using cognitive behavioral therapy for (CBT) health anxiety. Relatively few studies have been conducted in patients receiving care in hospitals. We conducted a randomized study in a hospital outpatient internal medicine clinic after a preliminary trial showed its efficacy. Methods We conducted a multicenter, randomized trial among patients with health anxiety attending cardiology, endocrinology, gastroenterology, neurology, and respiratory medicine clinics at a secondary care facility. We included patients aged 16-75 years who met criteria for excessive health anxiety, lived in the area covered by the hospital, and were not under investigation for a new pathology or were too unwell to participate in these investigations. We used a computer-generated randomization scheme to assign eligible medical patients to either the active treatment group (five to ten sessions of modified cognitive behavioral therapy delivered by a hospital therapist, CBT-HA group) or the outpatient standard of care group. The primary outcome was change in health anxiety symptoms as measured by the Health Anxiety Scale at 1 year, with the important secondary hypothesis of 2-year total health and social care cost equivalence, with an equivalence criterion of £150. Analyses were conducted by intention-to-treat. The study was registered at controlled-trials.com under ISRCTN14565822. Results Of the 28 991 patients we screened, 444 were randomly assigned to receive modified cognitive-behavioral therapy (CBT-HA group, 219 participants) or standard treatment (standard treatment group, 225 participants), respectively, with the CBT- 205 participants in the HA group and 212 participants in the standard treatment group were included in the primary endpoint analysis. At 1 year, patients in the CBT-HA group showed a 2?98-point improvement in health anxiety compared with the standard treatment group (95% CI 1?64-4?33, p<0?0001), and twice as many patients receiving cognitive-behavioral therapy achieved normal levels of health anxiety compared with the control group (13?9% vs. 7?3%; ratio 2?15, 95% CI 1?09-4?23, p=0?0273). A similar difference was observed at 6 months and 2 years, accompanied by a corresponding reduction in generalized anxiety and a decrease in depression. Of the nine deaths, six were in the control group; and all were due to preexisting conditions. There were no significant differences in social functioning or health-related quality of life between the two groups. Equivalent total 2-year costs were not achieved, but the differences were not statistically significant (corrected mean difference £156, 95% CI ?1446 to 1758, p=0?848). Interpretation of results The use of this form of modified cognitive-behavioral therapy for health anxiety elicited a sustained 2-year symptom benefit with no significant effect on total costs. It merits wider application in healthcare.