Synthetic arteriovenous grafts, an important option for hemodialysis vascular access, are prone to recurrent stenosis and thrombosis. Supplementation with fish oils has theoretical appeal for preventing these outcomes. To determine the effect of fish oil on synthetic hemodialysis graft patency and cardiovascular events. The Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) study, a randomized, double-blind, controlled clinical trial conducted at 15 North American dialysis centers from November 2003 through December 2010 and enrolling 201 adults with stage 5 chronic kidney disease (50% women, 63% white, 53% with diabetes), with follow-up for 12 months after graft creation. Participants were randomly allocated to receive fish oil capsules (four 1-g capsules/d) or matching placebo on day 7 after graft creation. Proportion of participants experiencing graft thrombosis or radiological or surgical intervention during 12 months' follow-up. The risk of the primary outcome did not differ between fish oil and placebo recipients (48/99 [48%] vs 60/97 [62%], respectively; relative risk, 0.78 [95% CI, 0.60 to 1.03; P = .06]). However, the rate of graft failure was lower in the fish oil group (3.43 vs 5.95 per 1000 access-days; incidence rate ratio [IRR], 0.58 [95% CI, 0.44 to 0.75; P < .001]). In the fish oil group, there were half as many thromboses (1.71 vs 3.41 per 1000 access-days; IRR, 0.50 [95% CI, 0.35 to 0.72; P < .001]); fewer corrective interventions (2.89 vs 4.92 per 1000 access-days; IRR, 0.59 [95% CI, 0.44 to 0.78; P < .001]); improved cardiovascular event-free survival (hazard ratio, 0.43 [95% CI, 0.19 to 0.96; P = .04]); and lower mean systolic blood pressure (-3.61 vs 4.49 mm Hg; difference, -8.10 [95% CI, -15.4 to -0.85]; P = .01). Among patients with new hemodialysis grafts, daily fish oil ingestion did not decrease the proportion of grafts with loss of native patency within 12 months. Although fish oil improved some relevant secondary outcomes such as graft patency, rates of thrombosis, and interventions, other potential benefits on cardiovascular events require confirmation in future studies. isrctn.org Identifier: ISRCTN15838383.