Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27-31% increase in risk of myocardial infarction and a 12-20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and show consistent risk across the trials. The fact that cardiovascular events were not primary endpoints of any of these studies will introduce noise but not bias into the data. A recent re-analysis of the Women's Health Initiative suggests that co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, on the function of vascular cells, and on blood coagulation. Calcium-sensing receptors might mediate some of these effects. Because calcium supplements produce small reductions in fracture risk and a small increase in cardiovascular risk, there may be no net benefit from their use. Food sources of calcium appear to produce similar benefits on bone density, although their effects on fracture are unclear. Since food sources have not been associated with adverse cardiovascular effects, they may be preferable. Available evidence suggests that other osteoporosis treatments are still effective without calcium co-administration.