OBJECTIVE: To evaluate the oropharyngeal red streak sign for diagnosing acute sinusitis. DESIGN: Exploratory cohort study. SETTING: A Veterans Affairs medical center urgent care center. PARTICIPANTS: Sixty consecutive subjects presenting with nasal symptoms lasting 4 weeks or less. MEASUREMENTS AND MAIN RESULTS: Each subject underwent a structured history and physical examination, followed by a sinus computed tomography (CT) scan. Acute sinusitis was defined by an air-fluid level or opacification of 1 or more sinuses on CT imaging. Twenty-seven subjects were diagnosed with sinusitis. A localized red streak in the lateral recess of the oropharynx was associated with sinusitis, with a positive likelihood ratio (LR+) and 95% confidence interval (CI) of 2.11 (1.23, 3.63) and a negative likelihood ratio (LR-) and 95% CI of 0.44 (0.24, 0.83). Opacity on maxillary or frontal sinus transillumination was also associated with sinusitis (LR+ of 1.89; CI 1.03, 3.32 and LR- of 0.56; CI 0.32, 0.96). Symptom duration > 10 days was associated with acute sinusitis with an LR+ of 1.89 (1.06, 3.59). A history of facial pain (LR+ of 0.59; CI 0.39, 0.90 and LR- of 2.85; CI 1.27, 6.41) and the finding of sinus percussion tenderness (LR+ of 0.22; CI 0.05, 0.90 and LR- of 1.88; CI 1.17, 3.03) were inversely associated with sinusitis. CONCLUSIONS: The oropharyngeal red streak may be an accurate physical sign for diagnosing acute sinusitis. This sign should be included in future studies of clinical diagnostic criteria for acute sinusitis.