Health-related quality of life (HRQOL) of 166 adults who had previously undergone surgical treatment for intractable epilepsy was compared with that of outpatients having hypertension, diabetes, heart disease, and/or depressive symptoms. Eight self-reported HRQOL domains were evaluated and compared using the RAND 36-Item Health Survey 1.0: emotional well-being, social function, role limitations due to emotional problems, energy/fatigue, pain, role limitations due to physical problems, physical function, and general health perceptions. A pictorial item on overall quality of life was also administered, for a total of nine HRQOL domains. Adjusting for age, gender, education, and co-morbid conditions, 55 completely seizure-free patients scored higher (i.e., better health) than patients with hypertension in six of nine domains, higher than diabetics in eight of nine, higher than those with heart disease in all nine, and higher than those with depressive symptoms in all nine (p's < 0.05). Sixty-seven patients still having seizures with impaired consciousness scored worse than hypertensives in five domains, diabetics in three, and heart disease patients in two; for all three conditions these domains included emotional well-being and overall quality of life (p's < 0.05). These 67 patients, however, scored better than patients with depressive symptoms in all nine domains, better than those with heart disease in two, and better than those with diabetes in one (p's < 0.05). Forty-four other patients had only simple partial seizures; their scores were comparable to those of diabetic and heart disease patients on mental and social health scales but were higher ("better") than these patients on physical health scales. In summary, HRQOL among patients who have undergone "curative" epilepsy surgery is better than that in patients who have hypertension, diabetes, heart disease, or depression. Patients who have continued seizures with loss of consciousness are worse off in terms of emotional well-being and overall quality of life than all other patients, except for those with depressive symptoms.