BACKGROUND: How to use clinical score, the rapid streptococcal antigen test (RSAT), and culture results is uncertain for efficient management of acute pharyngitis in adults. METHODS: This prospective cohort study included 372 adult patients with pharyngitis treated at a Swiss university-based primary care clinic. In eligible patients with 2 to 4 clinical symptoms and signs (temperature >or=38 degrees C, tonsillar exudate, tender cervical adenopathy, and no cough or rhinitis), we performed an RSAT and obtained a throat culture. We measured sensitivity and specificity of RSAT with culture as a gold standard and compared appropriate antibiotic use with cost per patient appropriately treated for the following 5 strategies: symptomatic treatment, systematic RSAT, selective RSAT, empirical antibiotic treatment, and systematic culture. RESULTS: RSAT had high sensitivity (91%) and specificity (95%) for the diagnosis of streptococcal pharyngitis. Systematic throat culture resulted in the highest antibiotic use, in 38% of patients with streptococcal pharyngitis. Systematic RSAT led to nearly optimal treatment (94%) and antibiotic prescription (37%), with minimal antibiotic overuse (3%) and underuse (3%). Empirical antibiotic treatment in patients with 3 or 4 clinical symptoms or signs resulted in a lower rate of appropriate therapy (59%) but higher rates of antibiotic use (60%), overuse (32%), and underuse (9%). Systematic RSAT was more cost-effective than strategies based on empirical treatment or culture: 15.00 dollars, 26.00 dollars, and 32.00 dollars, respectively, per patient appropriately treated. CONCLUSIONS: The RSAT we used is a valid test for diagnosis of pharyngitis in adults. A clinical approach combining this RSAT and clinical findings efficiently reduces inappropriate antibiotic prescription in adult patients with acute pharyngitis. Empirical therapy in patients with 3 or 4 clinical symptoms or signs results in antibiotic overuse.