The objective of this study was to determine if aspirin reduces the incidence of second eye involvement after nonarteritic anterior ischemic optic neuropathy (NAION) in one eye. Records were reviewed of 131 patients who sustained unilateral NAION. Of these, the 33 patients who sustained second eye NAION were compared to those followed for a minimum of 2 years without sustaining a second eye NAION (67). Thirty-one of the 131 patients were excluded because of inadequate follow-up. Except for diabetes (relative risk [RR] 1.43, p = 0.05), the incidence of second eye NAION was independent of gender, age, cup/disk, hypertension, anemia, and migraine. The degree of visual acuity or field dysfunction in the first eye correlated poorly with the acuity (r = 0.28) and field (r = 0.33) loss in the second eye. Aspirin (65-1,300 mg) taken two or more times per week decreased the incidence (17.5% vs. 53.5%) and relative risk (RR = 0.44, p = 0.0002) of second eye AION regardless of the usual risk factors. Even after eliminating those patients who had bilateral disease when first referred, ASA still reduced the incidence of second eye involvement (35% vs. 13%, RR = 0.74, p = 0.01). Aspirin may be an effective means of reducing second eye NAION.