PURPOSE: The validity of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to identify diagnoses of severe acute liver injury (SALI) is not well known. We examined the positive predictive values (PPVs) of hospital ICD-9-CM diagnoses in identifying SALI among health plan members in the Mini-Sentinel Distributed Database (MSDD) for patients without liver/biliary disease and for those with chronic liver disease (CLD). METHODS: We selected random samples of members (149 without liver/biliary disease; 75 with CLD) with a principal hospital diagnosis suggestive of SALI (ICD-9-CM 570, 572.2, 572.4, 572.8, 573.3, 573.8, or V42.7) in the MSDD (2009-2010). Medical records were reviewed by hepatologists to confirm SALI events. PPVs of codes and code combinations for confirmed SALI were determined by CLD status. RESULTS: Among 105 members with available records and no liver/biliary disease, SALI was confirmed in 26 (PPV, 24.7%; 95%CI, 16.9-34.1%). Combined hospital diagnoses of acute hepatic necrosis (570) and liver disease sequelae (572.8) had high PPV (100%; 95%CI, 59.0-100%) and identified 7/26 (26.9%) events. Among 46 CLD members with available records, SALI was confirmed in 19 (PPV, 41.3%; 95%CI, 27.0-56.8%). Acute hepatic necrosis (570) or hepatorenal syndrome (572.4) plus any other SALI code had a PPV of 83.3% (95%CI, 51.6-97.9%) and identified 10/19 (52.6%) events. CONCLUSIONS: Most individual hospital ICD-9-CM diagnoses had low PPV for confirmed SALI events. Select code combinations had high PPV but did not capture all events.