We examined the effect of soy isoflavones on bone density and strength in healthy postmenopausal women (45.8–65.0 y). Peripheral quantitative computed tomography (pQCT) measured 3 y change in cortical bone mineral density (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength‐strain index (SSI) at the 1/3 midshaft femur (N=165) and trabecular density (TbBMD), PC, and SSI at the 4% distal tibia (N=162) in response to soy protein‐extracted isoflavones (120 or 80 mg/d) or placebo. We report no treatment effect for femur CtThk, PC, or EC, or tibia PC. The 120 mg/d dose protected TbBMD, but high urinary phosphorus (UrP) (p<0.05) lessened this effect. High UrP negatively affected tibia SSI (p<0.05) in the 120 mg/d group. Also, the 120 mg/d dose protected femur CtBMD as time since last menstrual period increased (p<0.01) and the 80 mg/d dose protected femur SSI as bone turnover increased (p<0.05). Hence, soy isoflavones may exert a modest protective effect on pQCT measured bone parameters in postmenopausal women, but high UrP lessened this potential benefit. Supported by NIAMS/NIH (AR046922); NWRC, ISU; USDA/ARS, WHNRC; Clinical & Translational Science Center, CRC, UCD (1M01RR19975‐01); National Center for Medical Research (UL1 RR024146).