Instruction Set Simulation (ISS) is widely used in system evaluation and software development for embedded processors. Despite the significant advancements in the ISS technology, it still suffers from low simulation speed compared to real hardware. Especially for embedded software developers simulation speed close to real time is important in order to efficiently develop complex software. In this paper a novel, retargetable, hybrid simulation framework (HySim) is presented which allows switching between native code execution and ISS-based simulation. To reach a certain state of an application as fast as possible, all platform-independent parts of the application are directly executed on the host, while the platform dependent code executes on the ISS. During the native code execution a performance estimation is conducted. A case study shows that speed-ups ranging from 7× to 72× can be achieved without compromising debugging accuracy. The performance estimation during native code ex...