Objective: To assess the burden of mortality and hospitalized morbidity in newly treated epilepsy patients. Methods: We extracted relevant data of patients with newly treated epilepsy between September 16, 2005, and September 15, 2010, from the data repository covering all public hospitals in Hong Kong. Patients were followed up until September 15, 2011. Mortality and hospitalized morbidity were assessed, stratified by baseline comorbidities, number of antiepileptic drugs (AEDs) used, and treatment with enzyme-inducing AEDs (EIAEDs). Mortality was compared to the age-and sex-specific general population in Hong Kong. Results: Of the 7,461 newly treated epilepsy patients (55% male; median age 60 years), 2,166 (29%) died during the study period. The standardized mortality ratio was 5.09 (95% confidence interval [CI] 4.88-5.31), and was higher among those with physical or psychiatric baseline comorbidity (5.46; 95% CI 5.22-5.71) than those without (3.28; 95% CI 2.87-3.73). Standardized hospitalization ratio was 6.76 (95% CI 6.70-6.82). Baseline physical comorbidity-free patients (n 3,514) exhibited higher risk of developing stroke (standardized incidence ratio [SIR] 4.96; 95% CI 4.19-5.84) and ischemic heart disease (SIR 4.18; 95% CI 3.54-4.91), and male patients had elevated risk of developing cancer (SIR 2.30; 95% CI 1.75-2.97). Patients treated with EIAEDs had higher risk of being subsequently recorded with new physical comorbidities than those with non-EIAEDs (relative risk [RR] 1.48; 95% CI 1.19-1.85), especially for cerebrovascular disease (RR 1.78; 95% CI 1.14-2.77). Conclusions: Newly treated epilepsy patients bear excess mortality and hospitalization risks. They have higher risk of developing stroke, ischemic heart disease, and cancer. Treatment with EIAEDs was associated with increased overall morbidity.