The recent requirements for blending oxygenates with gasoline for pollution abatement and octane improvement have opened up huge markets for ethers, synthesized by catalytically reacting an isoolefin with an alcohol. Consequently, alternatives to isobutylene-derived methyl tert-butyl ether (MTBE) obtained from methanol and ethyl tert-butyl ether (ETBE) obtained from ethanol are being explored. This paper provides a thermodynamic analysis of the liquid-phase etherification of ethanol with 2-methyl-1-butene (2M1B) and 2-methyl-2-butene (2M2B), the two reactive isoamylene isomers. Both these isomers produce tert-amyl ethyl ether (TAEE) but also undergo isomerization. Theoretical and experimental results are provided here for the simultaneous TAEE synthesis and isoamylene isomerization. Expressions for the three thermodynamic equilibrium constants as a function of temperature are developed. Gibbs free energy and the enthalpy of formation of TAEE are also obtained. The equilibrium constants’ correlations are utilized to compute the effect of the feed mole ratio of the isoamylenes and the inert solvent to ethanol as well as the reaction temperature on the equilibrium conversions and selectivities. Conditions that maximize etherification conversion and selectivity are explored.