This study examines the effects of major life events, daily hassles and uplifts, and daily stress levels as they increase or decrease the risks of having seizures and estimates risk ratios for specific stressors and perceived stress levels. Utilizing a prospective design, 12 adults with severe epilepsy monitored the occurrence of seizures, stressors, and stress levels over a 3-month period. In within-individual analyses, high stress levels and stressful events were associated with more frequent seizures for most participants. The association between higher stress levels and increased seizures was confirmed in group analyses. This study provides empirical evidence of the association between stress and seizures and describes the use of a statistical model that is useful for investigating risk factors as they influence physical and mental illness.