Abstract Indoleamine 2,3 dioxygenase (IDO)1 and IDO2 are enzymes playing a pivotal role in the metabolism of tryptophan and in immune modulation. IDO2, in particular, was recently suggested to drive B cell-mediated autoimmune diseases. Two functional polymorphisms within the IDO2 gene are described that result in the production of enzymes with suppressed activity; we analyzed these polymorphisms in a cohort of Italian multiple sclerosis patients (MS). R248W (rs10109853) and Y359STOP (rs4503083) IDO2 polymorphisms were analyzed in 1355 Caucasian Italians (675 MS patients and 680 healthy controls) using Allelic discrimination Real-time approach with predesigned TaqMan probes. No significant differences in the distributions of rs10109853 and rs4503083 IDO2 polymorphisms could be observed between MS patients and the control group, even when patients were stratified according to disease phenotype (relapsing remitting - RRMS or primary progressive -PPMS) or sex. Moreover, the analyzed SNPs were not associated with age at onset or disease progression measured by EDSS (expanded disability status scale) and MSSS (multiple sclerosis severity score) scores. IDO2 rs10109853 and rs4503083 polymorphisms are not associated with MS risk, age at onset and disease progression in Italian MS patients.