Aromatase (CYP19A1) is a key enzyme that converts androgens to estrogens. Given its central role in estrogen biosynthesis, aromatase is a target of endocrine disruption. Aromatase disruption can be measured in vitro with cell-free enzyme assays or using cells expressing CYP19A1. Results may vary between models, as cell-based models can have adaptive responses not present in enzyme assays. Here, we have compared 21 chemicals for their ability to affect aromatase by direct and indirect disruption using an aromatase commercial kit and a modified H295R steroidogenesis assay. New data was generated for eighteen test compounds in either one or both of the models. Chemicals eliciting a response could be divided into five categories: 1) substances that decreased the response in both models, 2) substances that directly inhibited aromatase, but increased 17β-estradiol (E2) levels in H295R assay, 3) substances that directly inhibited aromatase, but did not affect E2 levels in H295R assay, 4) substances that did not inhibit aromatase activity, but increased E2 levels in the H295R model, and 5) substances that did not alter responses in either of the assays. These results illustrate that both assays are useful for assessing the potential of chemicals to affect E2 levels either through direct aromatase inhibition or other indirect mechanisms.