The goal of this numerical study is to investigate the effect of ultrasound waves on the entropy generation aspects in a water-cooled pin-fin heatsink. The effect of the number and locations of ultrasound transducers (32 different scenarios), Re number (500–2000) and frequency of ultrasound waves (F = 15–30 kHz) are investigated on the thermal and frictional entropy generation rates. It was revealed that different configurations with the transducers on two, three, and four walls entail a low thermal entropy generation rate, however, most of which have a high frictional entropy generation rate with the exceptions for case#27 and two other scenarios that bring a moderate frictional entropy generation rate. Therefore, case#27 was selected as the optimum configuration from the second thermodynamic law points of view. For the studied range of Re, the thermal entropy generation ratefor the optimum case is 21–47% lower than that for the base case at F = 30 kHz. While the frictional entropy generation rate for the optimum case escalates to 11–247 folds of the base case for Re numbers of 500–2000. In addition, the escalation of frequency from 15 to 25 kHz reduced the thermal and frictional entropy generation rates by 5.31% and 40.22%, respectively.