Background In nursing home residents, the use of tricyclic and other heterocyclic antidepressants is associated with an increased risk of falls. The newer selective serotonin-reuptake-inhibitor antidepressants are largely free of the side effects of the tricyclic agents thought to cause falls and so have been hypothesized to be safer for those at high risk for falls. Methods We retrospectively identified an inception cohort of 2428 nursing home residents in Tennessee who were new users of tricyclic antidepressants (665 subjects), selective serotonin-reuptake inhibitors (612 subjects), or trazodone (304 subjects) or nonusers of antidepressants (847 subjects). We ascertained the number of falls during therapy and during a similar follow-up period for nonusers, then calculated the rate ratios for fails with adjustments for an extensive set of potential confounding factors. Results The new users of each type of antidepressant had higher rates of falls than the nonusers, with adjusted rate ratios of 2.0 (95 percent confidence interval, 1.8 to 2.2) for tricyclic antidepressants, 1.8 (1.6 to 2.0) for selective serotonin-reuptake inhibitors, and 1.2 (1.0 to 1.4) for trazodone. The rate ratios increased with the daily dose for tricyclic antidepressants, reaching 2.4 (95 percent confidence interval, 2.1 to 2.8) for doses of 50 mg or more of amitriptyline or its equivalent, and for the serotonin-reuptake inhibitors, reaching 1.9 (1.7 to 2.2) for 20 mg or more of fluoxetine or its equivalent. The elevated rates of falls persisted through the first 180 days of therapy and beyond. Conclusions in this large study of nursing home residents, there was little difference in rates of falls between those treated with tricyclic antidepressants and those treated with selective serotonin-reuptake inhibitors. Hence, the preferential use of the newer antidepressants is unlikely to reduce the higher rate of falls among nursing home residents taking antidepressants. (N Engl J Med 1998;339:875-82.) (C)1998, Massachusetts Medical Society.