CONTEXT: Prior observational studies suggest that treatment with lithium may be associated with reduced risk of suicide in bipolar disorder. However, these studies are biased toward patients with the most severe disorders, and the relation to sex and age has seldom been investigated. OBJECTIVE: To investigate whether treatment with lithium reduces the risk of suicide in a nationwide study. DESIGN: An observational cohort study with linkage of registers of all prescribed lithium and recorded suicides in Denmark during a period from January 1, 1995, to December 31, 1999. SETTING: All patients treated with lithium in Denmark, ie, within community psychiatry, private specialist practice settings, and general practice. PARTICIPANTS: A total of 13 186 patients who purchased at least 1 prescription of lithium and 1.2 million subjects from the general population. MAIN OUTCOME MEASURE: All suicides identified on the basis of death certificates completed by doctors at the time of death. RESULTS: Patients who purchased lithium had a higher rate of suicide than persons who did not purchase lithium. Purchasing lithium at least twice was associated with a 0.44 reduced rate of suicide (95% confidence interval, 0.28-0.70) compared with the rate when purchasing lithium only once. Further, the rate of suicide decreased with the number of prescriptions of lithium. There was no significant interaction between continued lithium treatment and sex and age regarding the suicide rate. CONCLUSION: In a nationwide study including all patients treated with lithium, it was found that continued lithium treatment was associated with reduced suicide risk regardless of sex and age.