BACKGROUND: The effects of smoking and vascular risk factors (VRF) on relapse activity in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well understood. We aimed to investigate these. METHODS: MOGAD patients in the Oxford National Neuromyelitis Optica (NMO) Service with known smoking or VRF (hypertension, hypercholesterolaemia, type 2 diabetes, elevated body mass index) status were considered for inclusion. Outcomes were time-to-relapsing course and relapse rate. Cox and negative binomial regression were utilised. RESULTS: We included 172 patients. Current smokers had a 2.2 times higher relapse rate than never smokers (adjusted rate ratio 2.23 [95% CI = 1.35-3.68], p = 0.0017). Relapse rate was similar between past and never smokers (adjusted rate ratio 0.81 [0.51-1.29], p = 0.38). For time-to-relapsing course, multivariable analysis did not identify smoking as associated although univariable analysis showed a consistent trend with shorter time-to-relapse in current than never smokers (hazard ratio 1.76 [0.97-3.22], p = 0.06). There was no difference in either outcome by VRF status. CONCLUSION: Relapse rates were doubled in current than never smokers, whereas these were similar between past and never smokers. VRF did not associate with relapse risk. Smoking cessation should be encouraged in current smokers with MOGAD as past smokers were not observed with this poorer outcome.