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This paper deals with boiling heat transfer in the flow of water through an asymmetrically heated horizontal rectangular mini-channel. The mini-channel was made by gluing three transparent glass plates and a copper block. Through the glass window, the variable along the length of the mini-channel two-phase flow structures were recorded to determine local values of the void fraction. Four resistance heaters were attached to the copper block, powered by direct current, generating the heat initiating the flow boiling inside the channel. During the experiment, the following were measured: water volumetric flow rate, inlet pressure with pressure drop, inlet and outlet water temperature, copper block temperatures at three points inside its body, voltage and current supplied to the heaters. Stationary and laminar fluid flow with low Reynolds numbers were assumed in the mathematical model of heat transfer in selected elements of the measuring module. The temperature distributions in the copper block and flowing water were described by the appropriate energy equations: the Laplace equation for the copper block and the Fourier–Kirchhoff equation with parabolic fluid velocity for the flowing water. These equations were supplemented with a set of boundary conditions based on measurement data; moreover, data from experimental studies were the basis for numerical calculations and their verification. Two-dimensional temperature distributions of the copper block and water were calculated with the Trefftz method (TM). The main objective of this study was to determine the heat transfer coefficient on the contact surface of the copper block and water, which was calculated from the Robin boundary condition. The results of the calculations were compared with the results of numerical simulations performed using the Simcenter STAR-CCM+ software, obtaining consistent values. Computational fluid dynamics (CFD) simulations were verified based on experimental data including void fraction and temperature measurements of the copper block and flowing water.