Detailed microarchitectural simulators are not well suited for exploring large design spaces due to their excessive simulation times. We introduce AXCIS, a framework for fast and accurate design space exploration. AXCIS achieves fast simulation times by exploiting repetitions in program behavior to reduce the number of instructions simulated. For each dynamic instruction encountered during an initial full run of a benchmark, AXCIS builds an instruction segment, which concisely represents performance-critical information. AXCIS then compresses the string of dynamic segments into a table of canonical instruction segments (CIST) to give a compact representation of the entire benchmark trace. Given a precompiled CIST and a target microarchitecture configuration, AXCIS can quickly and accurately estimate performance metrics such as instructions per cycle (IPC). For the SPEC CPU2000 benchmarks and all simulated configurations, AXCIS achieves an average IPC error of 2.6%. While cycle-accurate simulators can take many hours to simulate billions of dynamic instructions, AXCIS can complete the same simulation on the corresponding CIST within seconds.