This paper presents the design optimization of LDMOSFET structures for use as power amplifiers in mobile wireless applications. A detailed study has been carried out to evaluate the influence of the device substrate on the RF performance. The performance of devices with bulk and Silicon-on-insulator (SOI) substrates has been compared for 50 V LDMOSFETs. In both cases, p-type and n-type epitaxial layers were considered. Extensive two-dimensional simulations have been performed to understand the device dynamics and to optimize the devices for better RF performance. A simple physics-based circuit model has been developed to enable large signal simulations for RF characterization. It is shown that bulk devices on n-type epitaxial layers yield the highest output RF power for a given voltage and current rating. SOI devices offer comparable RF performance with less area for a given rating, but suffer from self-heating effects. Thick-film SOI is shown as a viable power amplifier technology for integrated RFIC applications.