Background: Smoking increases the risk of multiple sclerosis (MS) and possibly disease progression. The reliability of self-reported smoking status is unknown in MS. We assessed the reliability of self-reported smoking status among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Methods: In 2004 and 2006, NARCOMS participants reported smoking status using Behavioral Risk Factor Surveillance Survey questions. We compared responses from 5,458 participants answering both questionnaires. We measured agreement regarding smoking status (ever/current) using a κ coefficient, and agreement for ages of starting and quitting smoking, and number of cigarettes smoked using an intraclass correlation coefficient (ICC). Results: In 2004, 2,885 (53.4%) participants reported ever smoking. The κ coefficient for ever smoking was 0.90 (95% confidence interval, CI: 0.89-0.92) and for current smoking 0.92 (95% CI: 0.90-0.94). The ICC for age at starting smoking was 0.73 (95% CI: 0.71-0.75) and for age at quitting smoking 0.90 (95% CI: 0.89-0.91). African-Americans, younger participants and those of lower socioeconomic status were less reliable. Depressed participants reported current smoking status less consistently (odds ratio: 0.51; 95% CI: 0.39-0.67). Conclusions: NARCOMS participants reliably report smoking status. The impact of depression on reliability of self-reported smoking status needs re-evaluation. Copyright © 2008 S. Karger AG.