This paper presents an experimental determination of Nusselt number (Nu(rs)) and friction factor (f(rs)) of heat exchanger tube with multiple square perforated twisted tape inserts. The effect of geometrical parameters, especially, perforation width ratio and twist ratio, has been investigated. The perforation width ratio (a/W-T) and twist ratio (T-L/W-T) have been varied from 0.083 to 0.333 and 2.0 to 3.5, respectively. The optimum values of parameters for multiple square perforated twisted tape inserts arrangement have been obtained and discussed. The effect of multiple square perforated twist tape inserts has been investigated for the range of Reynolds number (Re-n) from 5,000 to 27,000. The effect of important parameters on the Nu(rs) and f(rs) has been discussed, and the results are compared with the results of without square perforated multiple twisted tape inserts and smooth surface heat exchanger tube under similar flow conditions. The optimum values of parameters for multiple square perforated twisted tape inserts heat exchanger tube arrangement have been obtained and discussed. The maximum enhancement is observed at a a/W-T of 0.250 and T-L/W-T of 2.5, respectively.