OBJECTIVE: Eradication of Chlamydia pneumoniae infection and inhibition of elastolytic matrix metalloproteinases with doxycycline have been suggested to reduce the growth rates of small abdominal aortic aneurysms (AAA). We designed a study to investigate the efficacy of doxycycline in reducing the expansion of small AAAs. SUBJECTS AND METHODS: This was a prospective, double-blind, randomized, placebo-controlled study that was set in a university referral hospital. The study group consisted of 32 of 34 initially eligible patients who had an AAA diameter perpendicular to the aortic axis of 30 mm or more in size or a ratio of infrarenal to suprarenal aortic diameter of 1.2 or more and a diameter less than 55 mm. Patients were randomly assigned to receive either doxycycline (150 mg daily) or placebo during a 3-month period and underwent ultrasound surveillance during an 18-month period. Outcome measures included aneurysm expansion rates, the number of patients who had AAA rupture or repair, C pneumoniae antibody titers, and serum concentrations of C-reactive protein. RESULTS: The aneurysm expansion rate in the doxycycline group was significantly lower than that in the placebo group during the 6- to 12-month (P = .01) and the 12- to 18-month periods (P =.01). Five patients (41%) in the placebo group and 1 patient (7%) in the doxycycline group had an overall expansion of the aneurysm of 5 mm or more during the 18-month follow-up. Among the placebo group patients, a higher expansion rate was observed in those with enhanced C pneumoniae immunoglobulin G antibody titers (> 128) than in those with lower titers (P = .03). Doxycycline treatment had no clear effect on antibody titers. However, at 6-month follow-up, C-reactive protein levels in the doxycycline group were significantly lower than the baseline levels (P = .01). CONCLUSIONS: The results of this small pilot study suggest that doxycycline may favorably alter the outcome of patients with small AAA. However, because of the small size of this randomized study and of the potentially confounding effect of pretreatment risk factors, doxycycline-based treatment cannot be justified only on the ground of the current results. Because of the high prevalence of this disorder and its clinical, social, and economic relevance, a multicenter study should be performed to further investigate whether there is any place for medical treatment of small AAAs.