Many blood tests have been proposed as alternatives to liver biopsy for identifying fibrosis or cirrhosis. To evaluate the diagnostic accuracy of blood tests to identify fibrosis or cirrhosis in patients with hepatitis C virus (HCV) infection. MEDLINE (1947 to January 2013), the Cochrane Library, and reference lists. Studies that compared the diagnostic accuracy of blood tests with that of liver biopsy. Investigators abstracted and checked study details and quality by using predefined criteria. 172 studies evaluated diagnostic accuracy. For identifying clinically significant fibrosis, the platelet count, age-platelet index, aspartate aminotransferase-platelet ratio index (APRI), FibroIndex, FibroTest, and Forns index had median positive likelihood ratios of 5 to 10 at commonly used cutoffs and areas under the receiver-operating characteristic curve (AUROCs) of 0.70 or greater (range, 0.71 to 0.86). For identifying cirrhosis, the platelet count, age-platelet index, APRI, and Hepascore had median positive likelihood ratios of 5 to 10 and AUROCs of 0.80 or greater (range, 0.80 to 0.91). The Göteborg University Cirrhosis Index and the Lok index had slightly lower positive likelihood ratios (4.8 and 4.4, respectively). In direct comparisons, the APRI was associated with a slightly lower AUROC than the FibroTest for identifying fibrosis and a substantially higher AUROC than the aspartate aminotransferase-alanine aminotransferase ratio for identifying fibrosis or cirrhosis. Only English-language articles were included, and most studies had methodological limitations, including failure to describe blinded interpretation of liver biopsy specimens and inadequate description of enrollment methods. Many blood tests are moderately useful for identifying clinically significant fibrosis or cirrhosis in HCV-infected patients. Agency for Healthcare Research and Quality.