In this paper, dynamic simulations of the seasonal coefficient of performance (SCOP) of Air-Source Heat Pumps will be presented by considering three different heat pump systems coupled with the same building located in three different Italian municipalities: S. Benedetto del Tronto (42°58′ North, 13°53′ East), Milan (45°28′ North, 9°10′ East), and Livigno (46°28′ North, 10°8′ East). Dynamic simulations were conducted by employing the software package TRNSYS and by considering real weather data (i.e., outdoor air temperature and humidity as well as solar radiation) referring to the three abovementioned cities for a period of 8 years (2013–2020) and collected from on-site weather stations. Attention has been paid to the modeling of the heat pump defrost cycles in order to evaluate their influence on the unit’s seasonal performance. Results show that, when referring to different years, the thermal energy demand displays huge variations (in some cases it can even double its value), while the effective SCOP is characterized by scarce variability. Sensible variations in SCOP values are achieved for Livigno.