AbstractHeat exchangers have a wider scope in numerous applications, such as space heating, chemical industries, power stations, and so on. Due to heat loss and the thermal properties of the materials involved, the overall performance of a heat exchanger is questionable. Therefore, studies related to heat transfer techniques are appreciated in the research community. Thus, the present study numerically investigates the heat transfer performance of a horizontal heat pipe equipped with hexagonal perforated twisted tape inserts. Further, the numerical solutions of Nusselt number (Nu), friction factor (f), and thermal performance factor (TPF) are optimized with the help of response surface methodology (RSM). The parameters investigated in this study are Reynolds number (Re), which varies between 500 and 1500, input heat supply (Q) between 100 and 1000 W, and pitch ratio (3.2, 4, and 5.2). ANSYS fluid flow fluent was used to perform flow simulations for three different twisted tape inserts: horizontal, vertical, and alternate hexagon perforations. Optimum solutions are obtained at 1000 W heat supply, 1500 Re, and p/di = 4 from alternatively perforated twisted tape inserts. The optimum Nu, f, and TPF achieved are 119.545, 0.437, and 1.82, respectively. Also, the proposed RSM optimization method is evidenced with a maximum of 2.673% error during the confirmatory test.