Objective. To determine the prevalence of serious pathology in patients presenting to primary care settings with acute low back pain, and to evaluate the diagnostic accuracy of recommended "red flag" screening questions. Methods. An inception cohort of 1,172 consecutive patients receiving primary care for acute low back pain was recruited from primary care clinics in Sydney, Australia. At the initial consultation, clinicians recorded responses to 25 red flag questions and then provided an initial diagnosis. The reference standard was a 12-month followup supplemented with a specialist review of a random subsample of participants. Results. There were 11 cases (0.9%) of serious pathology, including 8 cases of fracture. Despite the low prevalence of serious pathology, most patients (80.4%) had at least 1 red flag (median 2, interquartile range 1-3). Only 3 of the red flags for fracture recommended for use in clinical guidelines were informative: prolonged use of corticosteroids, age >70 years, and significant trauma. Clinicians identified 5 of the 11 cases of serious pathology at the initial consultation and made 6 false-positive diagnoses. The status of a diagnostic prediction rule containing 4 features (female sex, age >70 years, significant trauma, and prolonged use of corticosteroids) was moderately associated with the presence of fracture (the area under the curve for the rule score was 0.834 [95% confidence interval 0.654-1.014]; P = 0.001). Conclusion. In patients presenting to a primary care provider with back pain, previously undiagnosed serious pathology is rare. The most common serious pathology observed was vertebral fracture. Approximately half of the cases of serious pathology were identified at the initial consultation. Some red flags have very high false-positive rates, indicating that, when used in isolation, they have little diagnostic value in the primary care setting.