Thyroid hormone (TH) is required for the metamorphosis of the long, coiled tadpole gut in Xenopus laevis into a shorter mature adult gut. Eleutherodactylus coqui, a direct developing frog, lacks a tadpole. Its embryonic gut is a miniature adult form with a mass of yolky endodermal cells attached to the small intestine to provide nutrition. The requirement of TH for the gut development in E. coqui was tested in this study. Inhibition of TH synthesis with methimazole arrested gut development in its embryonic form. T3, the active form of TH, induced gut development. Embryos treated with methimazole failed to utilize the yolk in their nutritional endoderm, and survived for weeks without any further development. Acidification of the yolk platelet is an initial step in the breakdown of yolk in X. laevis. E. coqui embryos in methimazole failed to acidify their yolk platelets, but acidification was stimulated by TH indicating its role in yolk utilization. In X. laevis, TRβ is upregulated in response to TH and induces differentiation of the adult gut. Similarly, EcTRβ, the E. coqui orthologue, was upregulated by TH in the gut. EcTRβ expression was high in the nutritional endodermal cells indicating a direct role for TH in yolk utilization. The low expression level of EcSox17, an endodermal transcription factor, in these nutritional endodermal cells was consistent with the fact that these cells did not contribute to the definitive gut. This study indicated a novel role for TH in yolk utilization in addition to its conserved role in gut development and differentiation