Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme that protects low-density lipoprotein (LDL) and HDL from peroxidation. In this study, PON1 activities were determined in patients with erectile dysfunction (ED) to investigate the relationship between ED and atherosclerosis. Forty patients, who had been diagnosed with ED by the medical and sexual anamnesis and routine laboratory tests, were included in the study. Thirty healthy, sexually active, married and age-matched men were selected as the control group. The patients and controls who underwent surgical or medical treatment in 1-week time and had a systemic disease such as malignancy, liver and renal insufficiency, and active infection and who smoked cigarettes were excluded. PON1 activities were measured spectrophotometrically. Unpaired samples t-test, correlation analyses and multiple linear regression analyses were used for statistical analyses. The results are given as mean+/-standard deviation of mean. The mean ages of the patient and the control groups were 31.05+/-6.90 (range 22-51) and 29.40+/-6.26 (range 19-46), respectively (P=0.307). Serum PON1 levels of the patient and the control groups were found to be 119.05+/-62.11 and 185.04+/-55.64, respectively. The difference between the groups was quite significant (P=0.001). Epidemiological and experimental studies indicate that PON1 activation was lower in individuals who had a tendency to develop atherosclerosis due to comorbidities such as diabetes, familial hypercholesterolemia and kidney disease. In this study, PON1 activity level was found to be significantly lower in ED patients than in control group. The decrease of PON1 activity may have a role in the ethiopathogenesis of ED, and the atherosclerosis development may be faster in the patients due to decreased activity of PON1, which is an antiatherogenic enzyme.