Multiple sclerosis (MS) is known to be influenced by various environmental factors including cigarette smoking. To identify the impact of smoking on conversion from clinically isolated syndrome (CIS) to clinically definite MS (CDMS), 95 consecutive uniformly treated smoker (n = 31) and nonsmoker (n = 64) CIS patients were evaluated retrospectively. The smoker CIS patients did not differ from nonsmokers by means of demographic and clinical findings. In addition, there was no difference between the two groups with respect to rate and time of conversion to CDMS. However, white matter lesions were detected in magnetic resonance imagings (MRIs) of all smoking versus 54 of 64 (63.5%) nonsmoking CIS patients (p = 0.02). Our results show that smoking does not predict conversion from CIS to CDMS. However, smoking may be associated with the appearance of white matter lesions on MRI at CIS onset.