The objective of this study was to compare costs, efficacy and cost efficacy of alternate oral antibacterial regimens for the ambulatory treatment of acute sinusitis. A public third-party perspective was adopted. The analysis was based on a decision tree and considered the episode of care from the decision to initiate an antibacterial until the end of the first course of treatment or the end of a subsequent course of treatment when needed. Efficacy data were retrieved from published clinical trials. Direct medical costs included the costs of physician visits, diagnostic tests and medications. The study pertained to adults treated in a primary-care setting in the Canadian province of Québec. The antibacterials studied were amoxicillin, amoxicillin/clavulanate, azithromycin, cefaclor, cefuroxime axetil and clarithromycin. The main outcome measured was the proportion of patients showing resolution or improvement of their symptoms. Initiating a treatment with amoxicillin was associated with similar efficacy and lower overall costs when compared with the other antibacterials. Low dosages of clarithromycin and azithromycin followed amoxicillin in terms of cost-efficacy ratio. This study confirms the place of amoxicillin as a first choice agent for acute sinusitis, with low dose clarithromycin and azithromycin as second choices.