Predicting a Table of Contents (TOC) pointer value responsive to branching to a subroutine. A subroutine is called from a calling module executing on a processor. Based on calling the subroutine, a value of a pointer to a reference data structure, such as a TOC, is predicted. The predicting is performed prior to executing a sequence of one or more instructions in the subroutine to compute the value. The value that is predicted is used to access the reference data structure to obtain a variable value for a variable of the subroutine.