Objective As patients with multiple sclerosis (MS) have more than 2.5-fold increased mortality risk, we sought to investigate the impact of tobacco smoking on the risk of premature death and its contribution to the excess mortality in MS patients.

Methods We studied 1032 patients during the period 1994–2013 in a UK-based register. Cox regression model was used to investigate the impact of smoking on the risk of premature death, controlling for confounders. Smoking-specific mortality rates were compared with the UK general population.

Results Of 923 patients with clinically definite MS, 80 (46 males and 34 females) had died by December 2012. HRs for death in current smokers and ex-smokers relative to never smokers were 2.70 (95% CI 1.59 to 4.58, p<0.001) and 1.30 (95% CI 0.72 to 2.32; p = 0.37). The standardised mortality ratio, compared with the UK general population, when stratified by smoking status was 3.83 (95% CI 2.71 to 5.42) in current smokers, 1.96 (95% CI 1.27 to 3.0) in ex-smokers and 1.27 (95% CI 0.87 to 1.86) in non-smokers. Never smokers and ex-smokers with MS had similar mortality rates compared with never smokers and ex-smokers without MS in the male British doctors cohort (1.12 (95% CI 0.63 to 1.97) and 0.54 (95% CI 0.26 to 1.14), respectively), while current smokers with MS had 84% higher rate of death compared with current smokers without MS (95% CI 1.24 to 2.72).

Conclusions Tobacco smoking can account for some of the excess mortality associated with MS and is a risk determinant for all-cause and MS-related death.