BackgroundThe effectiveness of long-acting injectable antipsychotics (LAIAs) has been demonstrated in studies using prescription claims data. However, the validity of claims data for LAIAs has not been established.ObjectiveWe aimed to validate date dispensed, quantity dispensed and days supplied fields in prescription claims data, and to compare claims- and medical record-derived persistence estimates.MethodsWe evaluated LAIA dispensations in the Drug Programs Information Network prescription claims database from Manitoba, Canada against a random sample of medical records. Adults with one or more LAIA prescription between April 2015 and March 2016 were eligible. Results were stratified by LAIA type (first-generation LAIA, risperidone LAI or paliperidone LAI). Persistence estimates were assessed using Kaplan–Meier survival analysis and proportion of patients covered method.ResultsClaims data had high positive predictive value, ranging from 80.0% (95% CI 51.9–95.7) to 100.0% (95% CI 89.7–100.0), but low negative predictive value, ranging from 0.0% (95% CI 0.0–2.5) to 62.5% (95% CI 40.6–81.2). Quantity dispensed and days supplied exactly matched dose and dosing interval, respectively, for 99.7% and 97.1% of risperidone LAI doses, 100.0% and 76.6% of paliperidone doses, and 8.9% and 28.3% of first-generation LAIA doses. There were no significant differences in claims-derived versus medical record-derived persistence estimates.ConclusionsQuantity dispensed and days supplied provide valid estimates of dose and dosing interval for second-generation LAIAs, but underestimated these parameters for first-generation LAIAs. However, a large proportion of medical record-confirmed doses were missing from claims data, and dose and dosing interval are underestimated in claims data.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00297-4.