Improving quality of life is the most important goal for patients with epilepsy. To recognize the factors associated with quality of life in patients with epilepsy in Mexico, we performed a cross-sectional survey using the Quality of Life in Epilepsy 31 (QOLIE-31) inventory to assess the quality of life of 401 adult patients with epilepsy at the National Institute of Neurology and Neurosurgery of Mexico. Clinical and demographical data were collected. Multiple regression was used to determine which factors affected quality of life in our patients. The variables that most strongly predicted a lower QOLIE-31 total score after multiple regression were sleep disorders (P<0.001), socioeconomic status (P<0.001), female gender (P=0.002), and high seizure frequency (P=0.001). In our study, neither depression nor time of evolution of epilepsy had significant influence on QOLIE-31 scores.