A non-responder heart failure patient to conventional cardiac resynchronization therapy (CRT) received novel mid-septal pacing (MSP) optimized CRT (MOT-CRT) by pacing at middle part of septum which captured both right and left ventricular septum in combination with coronary venous pacing (CVP). The QRS duration was shortened from 142 ms of the conventional CRT to 110 ms with improved cardiac function. MSP bypassed slow transseptal conduction and reduced 31 ms of left ventricular activation delay compared with right ventricular septal pacing. This case demonstrates for the first time that the MOT-CRT might serve as a valuable alternative to CRT.