The authors evaluated the association between multivitamin supplement use and breast cancer risk in a completed trial. At baseline (1992-1995), 37,920 US women aged > or =45 years and free of cancer provided detailed information on multivitamin supplement use. During an average of 10 years of follow-up, 1,171 cases of invasive breast cancer were documented. Multivitamin use was not significantly associated with overall risk of breast cancer. Compared with the risk for never users, the multivariable relative risks were 0.97 (95% confidence interval: 0.81, 1.16) for past users and 0.99 (95% confidence interval: 0.82, 1.19) for current users. Current multivitamin use for > or =20 years or > or =6 times/week was also not significantly associated with risk. Multivitamin use was nonsignificantly inversely associated with risk of breast cancer among women consuming > or =10 g/day of alcohol and with risk of estrogen receptor negative-progesterone receptor negative breast cancer. Multivitamin use was nonsignificantly associated with a reduced risk of developing < or =2-cm breast tumors but an increased risk of >2-cm tumors. The authors' data indicate no overall association between multivitamin use and breast cancer risk but suggest that multivitamin use might reduce risk for women consuming alcohol or decrease risk of estrogen receptor negative-progesterone receptor negative breast cancer.