Scanning with Malwarebytes Anti-Malware in safe or normal mode will work but removal functions are not as powerful in safe mode. Malwarebytes is designed to be at full power when malware is running so safe mode is not necessary when using it. In fact, Malwarebytes loses some effectiveness for detection & removal when used in safe mode because the program includes a special driver which does not work in safe mode. Further, scanning in safe mode prevents some types of malware from running so it may be missed during the detection process. Additionally, there are various types of malware infections which target the safeboot keyset so booting into safe mode is not always possible. For optimal removal, normal mode is recommended so it does not limit the abilities of Malwarebytes but sometimes there is no alternative but to do a safe mode scan. If that is the case, after completing a safe mode scan, reboot normally, update the database definitions through the program's interface (preferable method) and try rescanning again.
Microsoft MVP - Consumer Security 2007-2012 
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