Objective: The main purposes of this study were to validate the epilepsy diagnosis in incident epilepsy cases in the Danish National Patient Registry (DNPR), which contains information on nearly 9 000 000 individuals, and to identify persons in the validated cohort who fulfilled the International League Against Epilepsy (ILAE) criteria for drug‐resistant epilepsy (DRE). Methods: We reviewed a random sample of medical records from all individuals registered with a first diagnosis of epilepsy (International Classification of Diseases, 10th Revision [ICD‐10]: G40) or seizures (ICD‐10: G41, R56, or F445) in the Central Denmark Region from 2010 to 2019. In persons with a validated incident epilepsy diagnosis, we determined the proportion with DRE at the latest contact. We performed logistic regression analyses to identify clinical factors that correlated with risk of DRE. Results: Of 20 723 persons with a first diagnosis of epilepsy (n = 11 812) or seizures (n = 8911), we reviewed the medical records of n = 1067 with incident epilepsy and n = 610 with incident seizures. Among those with a register diagnosis of epilepsy, the diagnosis was confirmed in 838 cases (45% females, mean age at onset = 42.4 years), providing a positive predictive value (PPV) of 79% (95% confidence interval [CI] = 76%–81%). The PPV of focal epilepsy was 86% (95% CI = 82%–89%), and the PPV of generalized epilepsy was 71% (95% CI = 61%–80%). Of 740 patients with confirmed incident epilepsy and ≥1 year of follow‐up, 103 (14%) fulfilled the definition of DRE, 476 (64%) were drug responsive, and 161 (22%) had undefined responsiveness. In multivariable logistic regression analysis, early age at epilepsy onset, cognitive impairment, and a history of status epilepticus were associated with DRE. Significance: In the DNPR, we found a PPV of the epilepsy diagnosis of 79%. Among persons with confirmed epilepsy, 14% fulfilled ILAE criteria for DRE. Early age at epilepsy onset, cognitive impairment, and a history of status epilepticus were independently associated with drug resistance. [ABSTRACT FROM AUTHOR]