To determine the effect of long-term warfarin sodium therapy on quality of life, we surveyed 333 patients participating in a randomized, controlled trial of warfarin for the prevention of stroke in nonrheumatic atrial fibrillation. No significant differences between warfarin-treated and control patients were found on well-validated measures of functional status, well-being, and health perceptions. For example, the summary score for health perceptions was 68.8 in the warfarin-treated vs 66.6 in the control group (scale of 0 to 100; 95% confidence intervals for the difference, -1.6 to 6.0). In contrast, patients taking warfarin who had a bleeding episode had a significant decrease in health perceptions (-11.9; 95% confidence interval, -4.1 to -19.6). Warfarin therapy is not usually associated with a significant decrease in perceived health, unless a bleeding episode has occurred. Negative effects of warfarin treatment on health perceptions may be balanced by confidence in its protective effects.