The impact of smoking on microcirculation has been studied in small groups of subjects, preventing the evaluation of possible influences of smoker’s clinical characteristics or smoking habit variables on microcirculation. In order to fill this gap, we measured forearm skin blood flux under basal conditions and in response to ischemia in 100 current smokers (duration of smoking habit: 33.4 + 12.3 years), mean age 51 + 11 years (range: 8 to 86 yrs) consecutively enrolled at the smoking cessation clinic of the University Hospital of Pisa, and in 66 never-smoker controls matched by sex and age, using laser Doppler fluximetry (LDF). Information on smoking exposure and presence of other cardio-vascular risk factors were collected by standardised procedures. Skin post-occlusive reactive hyperaemia (PORH) was expressed as maximal post-ischemic flux (peak-flux) and as post-ischemic percentage change from baseline of the area under the LDF curve (AUC %). The skin LDF tracings were analysed in the frequency domain using an adapted version of Fourier analysis. Using this method we measured: the normalized (%) spectral power within 0.009-1.6 Hz total spectrum of the frequency intervals 0.009-0.02 Hz, related to endothelial-dependent skin vasomotion (SV); 0.021-0.06 Hz, related to sympathetic-dependent SV; 0.061-0.2 Hz, related to myogenic-dependent SV. Basal skin blood flux, peak-flux, AUC % and the sum of the normalized spectral power of endothelial-, sympathetic- and myogenic-dependent SV, were significantly lower (Wilcoxon test) in smokers than in non smokers (table). Smokers with at least one associated cardiovascular risk factor, such as arterial hypertension, diabetes or hypercholesterolemia, showed a significantly (p = 0.02) lower AUC %, compared to non-smokers. At the linear regression analysis, an inverse relationship was observed in smokers between AUC% and the smoking habit duration (r = 0.23, p = 0.018), age (r = 0.26, p = 0.008) and body mass index (r = 0.21, p = 0.037) of smokers. This study confirms that smoking is associated with microcirculatory impairment and shows that this impairment is negatively influenced by smoking habit duration, subjects’ age, BMI and presence of other cardiovascular risk factors.