The trade-off between efficient cooling and low power consumption is a goal that has always been very desirable in electronics cooling, especially nowadays that power densities of processing units are increasing. Conventional cooling solutions do not have the necessary cooling capacities for these power densities or require significant power consumption. In this study, a novel air-cooled thermosyphon cooling system for desktop computers is presented and experimentally tested. The thermosyphon comprises a vertical micro-channel cold plate as the evaporator and a horizontal air-cooled multiport coil as the condenser. The thermosyphon has a total height of 12 cm and operates with a fan speed of 1700 RPM. The working fluid selected for the thermosyphon loop is R1234ze(E), chosen for its advantageous thermophysical properties and nearly zero-GWP (Global Warming Potential). The test results presented in this paper aim to analyze thermosyphon’s thermal and hydraulic performance by studying the trends of thermal resistance and mass flow rate as a function of different operating conditions. The maximum heat rejection under safe conditions is 250 W, corresponding to a heat flux of about 18 W/cm2.