This report, the thirteenth of a series started in 2008, is a collection of 33 papers illustrating the main results obtained during 2021 using the CRESCO/ENEAGRID HPC facilities. The significant number of contributions proves the importance of the HPC facilities in ENEA for the research community. The topics cover various fields of research, such as materials science, efficient combustion, climate research, nuclear technology, molecular dynamics, plasma physics, biotechnology, complex systems physics, renewable energies, environmental issues, HPC technology. The report shows the wide spectrum of applications of high performance computing, which has become an all-round enabling technology for science and engineering. (go to report)