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BACKGROUND: Acute sinusitis-like complaints are very common and are usually treated with antibiotics in spite of the lack of evidence for the effectiveness of antibiotic therapy and the increasing number of resistant strains. AIM: To assess the effectiveness of doxycycline in adults with acute sinusitis-like complaints in general practice. METHOD: The effects of doxycycline in a placebo-controlled, double-blind, randomized trial were assessed in adults consulting their general practitioner (GP) with complaints after a common cold or influenza, pain in the head when bending forward, purulent nasal discharge, predominantly unilateral maxillary pain, toothache, or pain when chewing. Primary outcome events were the resolution of facial pain and the resumption of daily activities. Treatment differences were assessed by means of Kaplan-Meier curves and hazard ratios. The follow-up period was 42 days. RESULTS: No significant difference was found in time to recover between the doxycycline-treated group and the placebo-treated group. However, the adjusted hazard ratio for the group receiving doxycycline was 1.17 (95% CI = 0.87-1.57) for the resolution of pain and 1.31 (95% CI = 0.96-1.78) for the resumption of daily activities. After 10 days, 85% of all patients reported improvement and 60% were completely cured. Side effects were reported by 17% of the doxycycline-treated group, with two patients withdrawing because of side effects. CONCLUSIONS: Data from this study indicate that doxycycline does not add to the effectiveness of decongestive nose drops and steam inhalation in treating acute sinusitis-like complaints in general practice adults.