In the present study, the spectroscopic features of the radiolytic intermediates that were produced in gamma-irradiated (5, 10, 25 and 50kGy) sulfamethoxazole (SMX) have been investigated by electron spin resonance (ESR) spectroscopy and the radiation sterilization feasibility of SMX by ionizing radiation was examined. Gamma-irradiated SMX exhibited a complex ESR spectrum consisting of 13 resonance lines where spectral parameters for the central resonance line were found to be g=2.0062 and H-pp=0.6mT. The radiation yield of SMX was calculated to be relatively low (G=0.1) by ESR spectroscopy and no meaningful difference was observed in the comparison of unirradiated and 50kGy gamma irradiated SMX by the Fourier transform infrared (FT-IR) technique, confirming that SMX is a radioresistive material. Although SMX could not be accepted to be a good dosimetric material, the identification of irradiated SMX from the unirradiated sample was possible even for the low absorbed radiation doses and for a relatively long time (three months) after the irradiation process. Decay activation energy of the radical species, which is mostly responsible for the central intense resonance line, is calculated to be 45.15kJ/mol by using the signal intensity decay data derived from annealing studies. Four radical species with different spectroscopic properties were accepted to be responsible for the ESR spectra of gamma-irradiated SMX, by simulation calculations. It is concluded that SMX and SMX-containing drugs can be sterilized by gamma radiation and ESR spectroscopy is an appropriate technique for the characterization of these induced radical intermediates during the gamma irradiation process of SMX. Toxicology tests should also be done for its safe usage.