The correctness of a real-time system does not depend on the correctness of its calculations alone but also on the non-functional requirement of adhering to deadlines. Guaranteeing these deadlines by static timing analysis, however, is practically infeasible for current microarchitectures with out-of-order scheduling pipelines, several hardware threads, and multiple (shared) cache layers. Novel timing-analyzable features are required to sustain the strongly increasing demand for processing power in real-time systems. Recent advances in timing analysis have shown that runtime-reconfigurable instruction set processors are one way to escape the scarcity of analyzable processing power while preserving the flexibility of the system. When moving calculations from software to hardware by means of reconfigurable custom instructions (CIs)—additional to a considerable speedup—the overestimation of a task’s worst-case execution time (WCET) can be reduced. CIs typically implement functionality that corresponds to several hundred instructions on the central processing unit (CPU) pipeline. While analyzing instructions for worst-case latency may introduce pessimism, the latency of CIs—executed on the reconfigurable fabric—is precisely known. In this work, we introduce the problem of selecting reconfigurable CIs to optimize the WCET of an application. We model this problem as an extension to state-of-the-art integer linear programming (ILP)-based program path analysis. This way, we enable optimization based on accurate WCET estimates with integration of information about global program flow, for example, infeasible paths. We present an optimal solution with effective techniques to prune the search space and a greedy heuristic that performs a maximum number of steps linear in the number of partitions of reconfigurable area available. Finally, we show the effectiveness of optimizing the WCET on a reconfigurable processor by evaluating a complex multimedia application with multiple reconfigurable CIs for several hardware parameters.