The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is an ongoing randomized, double-blind, placebo-controlled, 2×2 factorial trial investigating whether taking a high-quality cocoa flavanol supplement or a multivitamin supplement reduces the risk of developing cancer, heart disease, and stroke. The trial has randomized 21,444 women aged 65 years and older and men aged 60 years and older throughout the United States. Ancillary studies will evaluate the effect of these supplements on cognitive function, macular degeneration and cataract, and other outcomes.