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Objective: To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea., Study Design: Double-blind randomized placebo-controlled trial., Population: The 416 patients included from 69 family practices were 12 years or older, presenting with acute upper respiratory complaints, and having a history of purulent rhinorrhea and no signs of complications of sinusitis., Outcomes Measured: Therapy success (disappearance of symptoms that most greatly affected the patient's health) at day 10 and duration of general illness, pain, and purulent rhinorrhea., Results: Therapy was successful in 35% of patients with amoxicillin and in 29% of patients with placebo (relative risk [RR] 1.14, 95% confidence interval [CI], 0.92-1.42). There was no effect on duration of general illness or pain. Duration of purulent rhinorrhea was shortened by amoxicillin (9 days vs 14 for clearing of purulent rhinorrhea in 75% of patients; P =.007). Diarrhea was more frequent with amoxicillin (29% vs 19%, RR 1.28, 95% CI, 1.05-1.57). No complications were reported. One patient (0.5%) receiving amoxicillin and 7 (3.4%) receiving placebo discontinued trial therapy because of exacerbation of symptoms (RR 0.25, 95% CI 0.04-1.56, P =.07). All 8 patients recovered with antibiotic therapy., Conclusions: Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery. The practical implication is that all such patients, whatever the suspected diagnosis, can be safely treated with symptomatic therapy and instructed to return if symptoms worsen.