OBJECTIVE: To evaluate the effect of soy isoflavones on menopausal symptoms in women who do and who do not produce equol, a daidzein metabolite. METHOD: A randomized, double-blind, placebo-controlled clinical trial was conducted over 6 months with 96 healthy menopausal women. After taking take 135 mg of isoflavones daily for 1 week, the women in the study group were assigned to the equol-producing (EP) or the non-EP group according to the presence or absence of equol in their urine. Menopausal symptoms were evaluated using a modified Kupperman Index. RESULT: Compared with the placebo group, the scores for hot flashes and excessive sweating were significantly reduced after 3 months, and the scores for weakness, palpitations, limb paresthesia, and total symptoms after 6 months, in the EP group only. CONCLUSIONS: Isoflavone supplementation improves menopausal symptoms only in women with the ability to produce equol.