Twenty healthy, asymptomatic long-term cigarette smokers (8 males, 12 females; mean age: 43 ±9 years) were selected at random from a larger series receiving nicotine replacement therapy (NRT) for 12 weeks to study the effects of NRT on plasma markers of oxidative stress. Plasma aliquots, obtained at baseline (T0) and after 12 weeks (T12) of NRT, were used to measure malondialdeyde (MDA) and total Trolox-equivalent antioxidant capacity (TEAC). In subjects who completely quit smoking (‘quitters’, n = 10), MDA was higher at T0 (1.08 μmol/l, interquartile range 0.85–1.16) than at T12 (0.71 μmol/l, range 0.32–0.92; p <0.01), and TEAC was lower at T0 (1.20 mM, range 1.11–1.31) than at T12 (1.43 mM, range 1.31–1.49; p <0.05). In subjects who had only reduced the number of cigarettes smoked per day (‘reducers’, n = 10), differences between the T0 and T12 levels of MDA (0.81 [0.75–0.96] vs. 0.76 [0.58–0.84] μmol/l) and TEAC (1.28 [1.05–1.50] vs. 1.25 [1.09–1.42] mM) were not significant. At T0, MDA and cotinine levels correlated in reducers (r = 0.79, p <0.05) and, though not significantly, in quitters (r = 0.50, p = 0.12). At T12 this relationship between MDA and cotinine was still present in the reducers (r = 0.70, p <0.05), while the scatter of points in quitters was completely dispersed (r = (0.09). These results show that smoking cessation but not smoking reduction is associated with decreased markers of oxidative stress in the plasma of active cigarette smokers.