One of the commonest questions I’m asked is whether RMXP is compatible with Windows Vista. The simple answer is "Yes and No". Rather than attempting to use RMXP on Vista (a better all-rounder in my opinion though it is), it’s better to use RMVX for Vista machines.
One of the problems with Vista is that it is extremely buggy and is known for its incompatibility issues. Running RMXP on Vista machines is possible, but not without endless hours tweaking certain system settings so that it can at least work half the time.
A common problem is that RMXP seems to work, but then suddenly freezes at any point (usually when playtesting games) or it will produce some obscure error message. Usually when this happens, it’s due to compatibility issues (either with the system itself or hardware conflicts).
One workaround is to make sure you have full Admin rights and change its permission to "Run compatibility mode for XP SP2". To set these options, this forum link will help. If there are any messages for updates, it’s probably prudent to download and install them.
To determine whether RMXP will be compatible with your Vista system, you can check at the Microsoft Compatibility Check. Hopefully this should help run RMXP on Vista machines.