This study proposes a novel high-flux pulsating heat pipe that can lift the major constraint of the conventional pulsating heat pipe (PHP) which is unable to function properly upon anti-gravity operations. The proposed PHP introduces additional unbalance force via uneven tube diameter/geometry in the adiabatic sections to tailor the problem in anti-gravity operation. The design contains a three-dimensional configuration circuitry with compact arrangement tubes on the evaporator and condenser. Through this design, the non-uniform three-dimensional pulsating heat pipe (3D-PHP) manipulates the uneven inner diameters of the adiabatic sections to form uneven vapor/liquid distributions in the adiabatic sections to yield a unitary flow pattern that is able to withstand a much higher input power. The present PHP uses methanol as working fluid, with 38% volumetric filling ratio, and has a high-flux of 22.9 W/cm(2)and a low the thermal resistance ratio (Ranti-gravity/Rgravity-assisted) of 1.05 when the input power is 800 W. Both the heat flux and thermal resistance ratio for the proposed design are far better than the existing literature.