Experimental, numerical and empirical research is carried out on pressure drop features of air-water two-phase flow in horizontal flattened tubes. Circular tubes of 10.5 mm I.D. made of copper were successively flattened into inner heights of 9, 8, and 6 mm (AR=1.27, 1.5, and 2.2, respectively). The experiment operation conditions were 200, 500, and 1000 kg/m2s for mass velocity, 6, 8, 10 LPM for flow rate, and 0 to 0.005 for gas quality. Also, the pressure drop for R134a and R410A was estimated numerically using ANSYS Fluent. The simulation test condi-tions were for vapor quality of 0.1 to 0.9 and saturation temperature of 40°C, while the condi-tions for mass velocity and flowrate are taken as that of the experiment test. The experimental data were examined to see how different factors affect on the pressure gradient. According to the outcomes and as compared to the circular tube, the pressure gradient was raised up to 27%, 95%, and 218% for tubes flattened with aspect ratio of 1.27, 1.5, and 2.2, respectively. More-over, the pressure drop for either air-water or refrigerant fluids is increased dramatically with increasing flow rate, but it decreases with increasing vapor quality. When compared to known circular tube correlations, a good agreement was achieved. Finally, the minimum difference between the experimental, numerical, and correlated results was less than 3% for gas quality of 0.0048 and aspect ratio of 2.2.