The presenting symptoms and rate of progression of multiple sclerosis (MS) are very heterogeneous. The diverse clinical manifestations and the clinical course of the disease may vary with modifiable risk factors. To systematically review modifiable risk factors and exposures associated with MS progression. We searched six databases till March 2015, reference-mined reviews, and consulted with experts (PROSPERO 2015:CRD42015016461). Two reviewers screened and extracted data.