Background: About 35% of patients with epilepsy may develop drug-resistant epilepsy (DRE). Identifying risk factors associated with DRE will allow us to identify earlier patients in the course of the disease. Methods: This is a case-control study nested within a cohort. Chart reviews of subjects who full fill inclusion criteria were completed. Inclusion criteria included age>18 years, focal epilepsy determined by clinical correlation and EEG. DRE was determined by ILAE criteria. Results: 149 subjects were included. Seventy had DRE (cases), and seventy-nine did not have DRE (controls). DRE group had a mean age of 41 years (SD+14.8) compared to the control group (49+17.5) (p=0.003). DRE group had a mean age at diagnosis of epilepsy of 19+15.3 compared to the control group with a mean of 33.6+21. (p=<0.001). The main risk factors identified in this study were; cortical dysplasia OR 8.67 (CI 1.04-72.3, p=0.026); mesial temporal sclerosis (MTS) (OR 2.69; CI 1.12-6.47; p=0.024); and presence of complex partial seizures (OR 2.04. Conclusions: Young age at diagnosis of focal epilepsy, diagnosis of cortical dysplasia, MTS, and presence of complex partial seizures are risk factors for DRE