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Background Few epidemiological studies have explored the effects of soil pollution on multiple sclerosis ( MS) risk in Asia. Method Based on catchment areas, Isfahan province is divided into five regions (Central, North, East, West, and South), and Soil sampling performed in catchment area with the highest range of MS prevalence and incidence. Samples were analyzed for cobalt (Co), lead (Pb), cadmium (Cd), copper (Cu), zinc (Zn), and absorbable forms of Pb, Cd, and Co. Linear regression is used to examine the association of soil heavy metals with prevalence of MS in central part of Isfahan province. Result Multiple sclerosis prevalence ranged from 5.62 to 156.65 in different townships. Based on regression analysis, in case of considering fixed amounts for the rest of elements, a one ( SD) increase of absorbable Pb and absorbable Cd are associated with 0.385 ( SD) ( P < 0.0001) increase and 0.209 ( SD) ( P < 0.007) decrease in MS prevalence, respectively. Conclusion This study documented a significant association between exposure to absorbable Pb and Cd in soil with prevalence of MS in Isfahan. Further work is warranted to confirm this association and if validated, to understand the mechanisms behind the association. [ABSTRACT FROM AUTHOR]