Objective: To estimate the effect of smoking on the risk for progression in multiple sclerosis (MS).

Methods: Self-reported data were used on smoking habits in 122 incident cases with disability assessments made after a median of 6 years disease duration.

Results: Ever smokers were more likely to have progressive disease compared with never smokers (P < 0.01). This was most pronounced in ever smokers with early smoking debut (< or = 15 years of age) for whom progressive disease was significantly more likely and occurred at an earlier age, compared with those with later smoking debut (P < 0.01 for both) or never smokers (P < 0.01 for both). Earlys moking start also predisposed to a progressive disease from onset when compared with never smokers (P = 0.012). A multivariate Cox regression analysis of sex, age at disease onset (above vs. under median) and smoking (ever vs. never) status showed that cases with late disease onset had three times higher risk and ever smokers had twice as high a risk for progression.

Conclusion: Past smoking is associated with a worsened prognosis in MS. The negative effect from smoking is most obvious in ever smokers with early smoking debut, which also affects MS phenotype significantly.