Numerical simulations are used to analyze the thermal performance of turbulent flow inside heat exchanger tube fitted with cross-cut twisted tape with alternate axis (CCTA). The design parameters include the Reynolds number (5000 < Re < 15; 000), cross-cut width ratio (0:7 < b=D < 0:9), cross-cut length ratio (2 < s=D < 2:5), and twist ratio (2 < y=D < 4). The objective functions are the Nusselt number ratio (Nu=Nus), the friction factor ratio (f =fs), and the thermal performance (g). Response surface method (RSM) is used to construct second-order polynomial correlations as functions of design parameters. The regression analysis shows that heat transfer ratio decreased with increasing both the Reynolds number and the width to diameter ratio of the twisted tape. This means that the twisted tape has more influence on heat transfer at smaller inlet fluid velocities. Sensitivity analysis reveals that among the effective input parameters, the sensitivity of Nu=Nus to the Reynolds number is the highest. The results reveal that thermal performance enhances with increasing the width to diameter ratio of the twisted tape (b=D). The maximum thermal performance factor of 1.531 is obtained for the case of Re = 5000; b=D = 0:9; s=D = 2:5, and y=D = 4.