BACKGROUND Soy foods contain several components (isoflavones and amino acids) that potentially affect bone. Few long-term, large clinical trials of soy as a means of improving bone mineral density (BMD) in late postmenopausal women have been conducted. OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and/or soy isoflavone consumption on skeletal health in late postmenopausal women. METHODS We conducted a randomized, double-blind, placebo-controlled clinical trial in 131 healthy ambulatory women aged >60 y. Ninety-seven women completed the trial. After a 1-mo baseline period, subjects were randomly assigned into 1 of 4 intervention groups: soy protein (18 g) + isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein + placebo tablets, control protein + isoflavone tablets, and control protein + placebo tablets. RESULTS Consumption of protein powder and isoflavone pills did not differ between groups, and compliance with the study powder and pills was 80-90%. No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers. However, there were significant negative correlations between total dietary protein (per kg) and markers of bone turnover (P < 0.05). CONCLUSIONS Because soy protein and isoflavones (either alone or together) did not affect BMD, they should not be considered as effective interventions for preserving skeletal health in older women. The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover. This trial was registered at ClinicalTrials.gov as NCT00668447.