BACKGROUND The rapid market expansion of filler treatment options requires physicians and health care providers to fully understand differences among comparable products. OBJECTIVE The objective was to compare commercially available polymethylmethacrylate (PMMA)-based soft tissue fillers to determine if there are meaningful variations in these products that could result in significantly different therapeutic profiles, especially with respect to safety. METHODS AND MATERIALS PMMA particles were evaluated for size and morphology using scanning electron microscopy (SEM) techniques. PMMA microsphere soft tissue filler products from the United States, Europe, Brazil, and Canada were compared with respect to size, homogeneity/irregularity, surface smoothness/roughness, and the presence or absence of sediment and particulate debris. RESULTS Marked differences with respect to PMMA particle morphology and related particle characteristics from a variety of products were found. Of note, some products demonstrated potentially concerning significant variability in particle size and irregular morphology. CONCLUSION It is anticipated that the variability detected in these products, based on the literature, could result in different therapeutic profiles, especially with respect to safety. Physicians and health care providers should be aware that "comparable" products that at a glance appear similar may not be equal.