PurposeAdverse drug reactions (ADRs) including medication allergies are not well-described among large national cohorts. This study described the most common documented medication allergies and their reactions among a national cohort of Veterans Affairs (VA) inpatients. MethodsWe evaluated inpatient admissions in any VA Medical Center from 1 January 2000 to 31 December 2014. Each admission was linked with allergy history preceding or upon admission. Individual drugs were aggregated into drug class category including: penicillins, sulfonamides, angiotensin converting enzyme (ACE) inhibitors, opiates, HMG-CoA reductase inhibitors (statins) and non-steroidal anti-inflammatory inhibitors (NSAID). Results were reported in aggregate and over time. ResultsApproximately 10.8 million inpatient admissions occurred from 2000 to 2014. We found the most commonly reported allergy drug classes were penicillins (13%, n=1410080), opiates (9.1%, n=984978), ACE inhibitors (5.7%, n=618075) sulfonamides (5.1%, n=558653), NSAIDs (5.1%, n=551216) and statins (3.6%, n=391983). Several allergy histories increased over time including opiates (6.2 to 11.2%), ACE inhibitors (1.3 to 10.2%), statins (0.3 to 7.3%) and NSAIDs (3.9 to 6.0%). Rash was the most commonly documented reaction on reports for penicillins (25.5%, n=371825), sulfonamides (25.6%, n=165954) and NSAIDs (10.3%, n=65741). The most common reaction for opiates was nausea/vomiting (17.9%, n=211864), cough/coughing for ACE inhibitors (41.0%, n=270537) and muscle pain/myalgia for statins (34.1%, n=186565). ConclusionsWe report that penicillins and opiates are the most commonly documented drug allergies among VA inpatients, but other drug classes such as ACE inhibitors, statins and NSAIDs are becoming increasingly common. Clinicians also commonly document non-allergic ADRs in the allergy section such as cough or myalgia. Copyright (c) 2016 John Wiley & Sons, Ltd.