At the end of your message when you talk about restarting systems, it sounds like you are dealing with two machines - is that the case? The Qbooks is on a system other than the CF server? In that case you need to make sure that CF is not running as the (default) service account, because that account cannot do network accesses. Same problem as if you were trying to do a CFFILE or CFDIRECTORY to a UNC. If you have CF installed with the default settings, then create a new admin account, and then go into the SERVICES menu and change each of the CF components (especially the ODBC services) to use that account for their login account. You might (depends on your networking setup and OSes involved) also have to work on the access prives for the share drive on the system running QBooks so that the server running CF can get to it. The reason that it seems to be working when you do the test from Windows ODBC is that at that point it is accessing the server running QBooks using whatever login account you (not CF) are currently logged into.
They are on two separate machines but they are not on the same network. The datasource is setup using QODBC driver with iBiz remote connector. It is connecting to an IP address on a port like http://22.214.171.124:2080. We have a few other datasources setup that point to an IP address as well that have no problem connecting in Coldfusion and those are using the ODBC Socket driver type as well. Would this still be an issue?