The microbial degradation of thiodiglycol, the primary hydrolysis product of sulfur mustard, by a pure culture of Alcaligenes xylosoxydans ssp. xylosoxydans (SH91) was accomplished in laboratory scale stirred tank reactors. This is a major component of the overall biodegradation process proposed for the complete mineralization of sulfur mustard. Several configurations were evaluated for degradation efficiency including batch, repeated batch, continuous stirred tank reactor (CSTR), and two-stage series CSTR. The repeated batch reactor provided the highest degradation rate of thiodiglycol. Further, this method degraded thiodiglycol in the liquid broth to below the detection limits (0.03 mM). Both batch and repeated batch experiments were simulated by an unstructured mathematical model. Simulation results were in agreement with the experimental data, particularly at low TDG concentration (around 30 mM). This study demonstrates the degradation of thiodiglycol using bioreactors and, more generally, is an experimental study of bioreactor designs for the degradation of growth-inhibitory substances.