The pads (nopales) of the prickly pear cactus are considered to be a good source of minerals and other nutrients on the basis of compositional analysis. In this study, this analysis is taken a step further by assessing the availability of selected minerals in nopales using an in vitro digestion and dialysis method. The results obtained suggest that although nopales are enriched in a number of minerals, their tissue calcium is not freely available. Microscopic analysis, energy-dispersive X-ray microanalysis, and oxalate measurements suggest that this reduction in available calcium is a result of its sequestration in the form of calcium oxalate crystals. The issue of mineral availability in plant foods is important when the dependence of many populations around the world on plant foods as their main source of minerals and other nutrients is considered.