Shell and tube heat exchanger with single twisted tube bundle in five different twist angles, are studied using computational fluid dynamics (CFD) and compared to the conventional shell and tube heat exchanger with single segmental baffles. Effect of shell-side nozzles configurations on heat exchanger performance is studied as well. Heat transfer rate and pressure drop are the main issues investigated in the paper. The results show that, for the same shell-side flow rate, the heat transfer coefficient of heat exchanger with twisted tube bundle is lower than that of the heat exchanger with segmental baffles while shell-side pressure drop of the former is even much lower than that of the latter. The comparison of heat transfer rate per unit pressure drop versus shell-side mass flow rate shows that heat exchanger with twisted tube bundle in both cases of perpendicular and tangential shell-side nozzles, has significant performance advantages over the segmental baffled heat exchanger. Optimum bundle twist angles for such exchangers are found to be 65 and 55° for all shell side flow rates.