Background and purpose: The modifiable risk factor cigarette smoking has been associated with an increased risk of developing multiple sclerosis (MS) and with disease activity in relapsing -remitting MS. However, less is known about the effect of smoking on disease progression in progressive MS. Here the association between cigarette smoking and disability accumulation in primary progressive MS (PPMS) is investigated. Methods: Kaplan-Meier survival analyses and Cox proportional hazard modelling were used to investigate the influence of cigarette smoking on the risk of reaching Expanded Disability Status Scale (EDSS) 4 and 6 as well as the time from EDSS 4 to 6 in patients with PPMS. Results: In all, 416 patients with PPMS and available smoking history were identified. Median time to EDSS 4 was 4 years in ever-smokers and 5 years in never-smokers (P = 0.27), and it was 9 years to EDSS 6 in both ever-smokers and never-smokers (P = 0.48). Smokers were not at increased risk of faster progression to EDSS 4, 6 and from EDSS 4 to 6. Age at disease onset was the strongest risk factor for progression to EDSS 4, 6 and from EDSS 4 to 6. Conclusions: Our investigation of a large and well-characterized population based PPMS cohort suggests that cigarette smoking does not influence disability accumulation in PPMS. Our findings support the idea that PPMS is driven by different underlying pathomechanisms than relapsing -remitting MS.