The predicted indirectly recognizable human leucocyte antigen (HLA) epitopes (PIRCHE) algorithm is a novel in silico algorithm to determine donor–recipient compatibility. The PIRCHE algorithm determines donor–recipient compatibility by counting the number of mismatched HLA‐derived epitopes that are involved in indirect T‐cell alloimmune responses; these epitopes are designated as PIRCHE. Over the last few years, the PIRCHE algorithm has been investigated in both hematopoietic stem cell transplantation and solid organ transplantation. This review describes the theory of the algorithm, its application in transplantation, and highlights the future perspectives on the clinical application of the PIRCHE algorithm.