Experimental and clinical evidence suggests that long-chain n-3 fatty acids may protect against sudden cardiac death, the leading cause of mortality in hemodialysis patients. Here we investigated whether long-chain n-3 fatty acids have a protective relationship with sudden cardiac death in 100 patients who died of sudden cardiac death during the first year of starting hemodialysis and 300 patients who survived. Individuals were selected from a nationally representative cohort of over 1000 US hemodialysis units in 2004-2005. The odds of sudden cardiac death were calculated by quartile of long-chain n-3 fatty acid levels over the first year. There was a significant inverse relationship between long-chain n-3 fatty acids and the risk of sudden cardiac death even after adjusting for relevant comorbid conditions, biochemical values, and dietary fats. The odds of sudden cardiac death at 1 year for the second, third, and fourth quartile groups of long-chain n-3 fatty acids were 0.37, 0.22, and 0.20, respectively, compared with the lowest quartile. This significant inverse relationship was maintained even during the highest-risk first few months on hemodialysis. Thus, long-chain n-3 fatty acids are strongly and independently associated with a lower risk of sudden cardiac death in hemodialysis patients throughout the first year of hemodialysis.