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Identification of patients with nonalcoholic fatty liver disease (NAFLD) who have advanced fibrosis is crucial. Vibration controlled transient elastography (VCTE) is an alternative to biopsy, although published experience with VCTE in a US population is limited.We performed a prospective cohort of 164 biopsy-proven NAFLD patients evaluated with VCTE using an M probe and the NAFLD fibrosis score (NFS) at baseline and a repeat VCTE at 6 months. Reliable liver stiffness measurements (LSMs) were defined as 10 valid measurements and interquartile range ≤30% of the median.A total of 120 (73.2%) patients had reliable LSM. The median LSMs for patients with and without F3–F4 (advanced) fibrosis were 6.6 kPA (5.3–8.9) and 14.4 kPA (12.1–24.3), respectively. The optimal LSM cutoff for advanced fibrosis was 9.9 kPA (sensitivity 95% and specificity 77%). In addition, 100% of patients with LSM<7.9 kPA did not have advanced fibrosis. A risk stratification strategy based on VCTE avoids the need for biopsy in at least the 74 (45.1%) patients correctly classified as low risk for advanced fibrosis. For the detection of F3–F4 fibrosis in patients with reliable VCTE, the area under the receiver operating curve (AUROC) is 0.93 (95% CI: 0.86–0.96). This is superior to the AUROC for the NFS (0.77),P=0.01. Patients who achieved a ≥5% weight loss at 6-month follow-up experienced improved LSM (P=0.009), independent of the changes in aminotransferase levels.Reliable VCTE results can rule out advanced fibrosis and avoid the need for biopsy in at least 45% of US patients with NAFLD. However, 1 in 4 patients have uninterpretable studies using the M probe.