Programs that are being re-hosted from the mainframe to Enterprise Server can be fully migrated to a 64-bit environment; although, those programs that are simply being moved from the mainframe for development and testing purposes should remain 32-bit compatible programs, because the IBM mainframe COBOL only supports 32-bit.
The COBOL and PL/I language syntax is capable of running in a 64-bit environment, but if the programs being migrated include third-party components, for example ADABAS or Easytrieve, you should consult those vendors to see if they are compatible in a 64-bit environment before any migration work is carried out.
As discussed in Programs Using Pointers, a change in pointer size can be problematic if certain assumptions on size are made within the code. Historically, mainframe programmers often took advantage of the relaxed syntax rules for redefining data that COBOL afforded, as it often reduced the amount of code required to be written. Therefore, running the 64 bit readiness rule set from within the IDE or as part of the Enterprise Analyzer product is highly recommended.
You should also set the AMODE directive, which can help you switch between 32- and 64-bit environments for programs performing arithmetic on mainframe-style pointers.