A system and method for efficiently performing program instrumentation. A processor processes instructions stored in a memory. When the processor processes a given instruction of a given instruction type, the processor updates a corresponding performance counter. When the performance counter reaches a threshold, the processor generates an interrupt and compares a location of the given instruction with stored locations in a given list. If a match is not found, then the processor processes an instruction following the given instruction in the computer program without processing intermediate instrumentation code. If a match is found, then the processor processes instrumentation code. Regardless of whether or not the instrumentation code is processed, when control flow returns to the computer program, the corresponding performance counter is initialized with a random value.