Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and mere are limited data from patients widi HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model Based on this, a simple index (FIB-4) was developed: age ([yr] × AST [U/L]) I ((PLT [10 9 /L]) × (ALT [U/L]) 1/2 ). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of < 1.45 in the validation set, the negative predictive value to exclude advanced fibrosis (stage 4-6) was 90% with a sensitivity of 70%. A cutoff of > 3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients. Copyright © 2006 by the American Association for the Study of Liver Diseases.