AbstractBackgroundIn order to compute the relative biological effectiveness (RBE) of ion radiation therapy with the Mayo Clinic Florida microdosimetric kinetic model (MCF MKM), it is necessary to process entire microdosimetric distributions. Therefore, a posteriori RBE recalculations (i.e., for a different cell line or another biological endpoint) would require whole spectral information. It is currently not practical to compute and store all this data for each clinical voxel.PurposeTo develop a methodology that allows to store a limited amount of physical information without losing accuracy in the RBE calculations nor the possibility of a posteriori RBE recalculations.MethodsComputer simulations for four monoenergetic12C ion beams and a12C ion spread‐out Bragg peak (SOBP) were performed to assess lineal energy distributions as a function of the depth within a water phantom. These distributions were used in combination with the MCF MKM to compute the in vitro clonogenic survival RBE for human salivary gland tumor cells (HSG cell line) and human skin fibroblasts (NB1RGB cell line). The RBE values were also calculated with a new abridged microdosimetric distribution methodology (AMDM) and compared with the reference RBE calculations using the entire distributions.ResultsThe maximum relative deviation between the RBE values computed using the entire distributions and the AMDM was 0.61% (monoenergetic beams) and 0.49% (SOBP) for the HSG cell line, while 0.45% (monoenergetic beams) and 0.26% (SOBP) for the NB1RGB cell line.ConclusionThe excellent agreement between the RBE values computed using the entire lineal energy distributions and the AMDM represents a milestone for the clinical implementation of the MCF MKM.