The purpose of the present parallel-design, controlled clinical trial was to evaluate the treatment outcome following flap debridement surgery (FDS) procedures in smokers compared to non-smokers. 58 systemically healthy subjects with moderate to advanced periodontitis, who presented one area (3 to 6 teeth) with persisting diseased sites after initial therapy, were selected. 29 patients (mean age: 39.7 years, 20 males) were smokers, while 29 patients (mean age: 43.9 years, 7 males) were non-smokers. Full-mouth plaque (PlI) and Bleeding on Probing (BoP) scores, probing depth (PD) and clinical attachment level (CAL) were assessed immediately before surgery and at 6 months postsurgery. PlI and BoP scores significantly decreased in both smokers and non-smokers. PD reduction and CAL gain were greater in non-smokers (2.4  0.9 mm and 1.6  0.7 mm, respectively) than in smokers (2.0  0.9 mm and 1.2  0.8 mm, respectively), however these differences did not reach the statistical significance. When sites presenting baseline PD  7 mm were considered, smokers showed significantly less PD reduction (3.1  1.1 mm) and CAL gain (1.9  1.2 mm) compared to non-smokers (3.9  0.8 mm and 2.8  1.0 mm, respectively). In smokers, there was a significant difference in mean CAL change in patients with exposure >15 packs/years (0.9  0.5 mm) compared to those with lower exposure (1.5  0.8 mm). The results of this study suggest that healing outcome following FDS procedures is impaired in cigarette smokers. This study was partly supported by MURST grant #97/60/06/014.