Microsurgeons suspect that cigarette smoking reduces the survival of free vascularized flaps and replantations, but this has never been proven. This experimental study investigates the effect of smoking on free-flap survival. A fasciocutaneous epigastric flap was used in 30 rats as a free flap and in 30 rats as a pedicled flap. Of each group, 10 rats were smoked 6 weeks before and 2 weeks after surgery, 10 rats were smoked only 6 weeks before surgery, and 10 rats underwent the sham smoking procedure. Also, a distally based dorsal skin flap was cut in all rats, representing a random vascularized flap. Vitality and size of both flaps and patency of the vascular anastomoses were assessed 14 days after surgery. The epigastric flaps were monitored by laser Doppler flowmetry and thermometry during the experiment. Survival of the free vascularized epigastric flaps was significantly lower in smoking rats. All pedicled flaps except one survived. The epigastric flaps only necrosed or survived completely, exactly correlating to the patency of the vascular anastomoses. The mean surviving area of the dorsal flaps was best for nonsmoking rats, worse for only preoperatively smoking rats, and worst for preoperatively and postoperatively smoking rats. The differences were statistically significant. Postoperative laser Doppler flow differed significantly between surviving and dying flaps, affirming the value of laser Doppler flow monitoring in microvascular surgery. In conclusion, this study proves that smoking of cigarettes is detrimental to the survival of free vascularized flaps.