A closed-loop pulsating heat pipe made of a copper tube (1.1 mm/2 mm I.D./O.D.) and filled with FC-72 has been tested in a large-diameter centrifuge (LDC) of the European Space Agency in Noordwijk at different hypergravity levels up to 20 g, different heat input levels, and different orientations with respect to the gravity direction (vertical bottom heated and horizontal position). The results show that both in the horizontal and vertical orientation the device operation depends on the combined effect of gravity and heat input level. For the horizontal orientation, fluid stratification and the consequent thermal crisis occur at different acceleration levels depending also on the heat input power level and on the heating/gravity history. During the vertical operation, the pulsating heat pipe (PHP) thermal performance is slightly enhanced by the lower hypergravity levels (up to 3 g at 50 W, up to 4 g at 70 W, and up to 6g at 100 W), while two different local thermal crises affect the PHP thermal behavior at higher acceleration levels