A method and system are provided for adaptively modeling and simulating high speed response of a transmission line. A simulation unit maintains a plurality of curve approximation options for modeling the transmission line. The suitability of a predefined primary one of the curve approximation options for modeling is determined based on frequency-domain modal scattering parameters obtained according to frequency-dependent data characterizing the transmission line. One of the options is selectively executed in response to the determination, in order to generate a macromodel of the transmission line. The primary option is executed upon determination of suitability, while a secondary one of the curve approximation options is alternatively executed upon determination of non-suitability. Transient simulation is then executed upon the resulting macromodel of the transmission line.