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Performing analysis across module boundaries for an entire program is important for exploiting several runtime performance opportunities. However, due to scalability problems in existing full-program analysis frameworks, such performance opportunities are only realized by paying tremendous compile-time costs. Alternative solutions, such as partial compilations or user assertions, are complicated or unsafe and as a result, not many commercial applications are compiled today with cross-module optimizations. We present SYZYGY, a practical framework for performing efficient, scalable, interprocedural optimizations. The framework is implemented in the HP-UX Itanium® compilers and we have successfully compiled many very large applications consisting of millions of lines of code. We achieved performance improvements of up to 40% over optimization level two and compilation time improvements in the order of 100% and more compared to a previous approach.