Purpose Radioisotopes such as 75 Se, 169 Yb and 153 Gd have photon energy spectra and half-lives that make them excellent candidates as alternatives to 192 Ir for high dose rate brachytherapy. The aim of this study was to evaluate the relative biological effectiveness (RBE) of current ( 192 Ir, 125 I, 103 Pd) and alternative ( 75 Se, 169 Yb, 153 Gd) brachytherapy radionuclides using Monte Carlo (MC) simulations of lineal energy distributions. Materials and Methods Brachytherapy sources microSelectron v2 ( 192 Ir, 75 Se, 169 Yb, 153 Gd), SelectSeed ( 125 I) and TheraSeed ( 103 Pd) were placed in the center of a spherical water phantom with a radius of 40 cm using the Geant4 MC simulation toolkit. The kinetic energy of all primary, scattered and fluorescence photons interacting in a scoring volume were tallied at various depths from the source. Electron tracks were generated by sampling the photon interaction spectrum, and tracking all the interactions down to 10 eV using the event-by-event capabilities of the Geant4-DNA models. The dose mean lineal energy ( y ¯ D ) values were obtained through random sampling of transfer points and overlaying spherical scoring volumes within the associated volume of the tracks. The scoring volume diameter was determined by fitting the y ¯ D -ratio for 125 I to its observed RBE. Results y ¯ D increased with increasing distance from the source for 192 Ir, 75 Se, and 169 Yb, remained constant for 153 Gd and 125 I, and decreased for 103 Pd. The diameter at which the y ¯ D -ratio coincided with the RBE of 1.15-1.20 for 125 I was about 25-40 nm. The RBE (reference 1 MeV photons) at high doses and dose rates for 192 Ir, 75 Se, 169 Yb, 153 Gd, 125 I and 103 Pd were 1.028-1.034, 1.05-1.07, 1.12-1.15, 1.16-1.21, 1.15-1.20, and 1.17-1.22, respectively. Conclusions The radiation quality of the radionuclides under investigation are higher than that of high energy photons. This study has provided a set of values to modify prescription doses for brachytherapy treatments to account for the variation in radiation quality between radionuclides.