The rising trend in cardiovascular disease is made evident by the drastic increase in health care costs as more and more people seek medical attention for coronary heart disease, atherosclerosis, heart attack, and stroke. This disease is further exacerbated by cigarette smoking which increases inflammation and has been proven to cause cancer. The focus to combat this disease has shifted away from treatment and towards prevention as people are realizing the benefits of exercise on all aspects of health. While the benefits of aerobic exercise are well-documented, resistance training (RT) as a means to counteract the markers of cardiovascular disease is not as well understood. The current study exams the effect of a 12-week periodized RT intervention and nicotine replacement therapy (NRT) on the fitness level and body composition in a population of young sedentary smokers. The subjects were randomized into four groups: RT and NRT, only RT, only NRT, or into the control group which received neither RT nor NRT. Participants were young (age 24.5 ± 4.6 yr), sedentary smokers. The control group had no significant drop in BMI and weight compared to the RT/NRT and RT groups. The RT/NRT group had a significant decrease in total fat, trunk fat, and fat percentage. The RT group had a significant increase in CRF measures compared to the other groups. Relative maximum aerobic capacity increased from 27.4 ± 3.05 ml/kg/min to 30.8 ± 2.12 ml/kg/min. This was significantly greater than the improvement seen in the NRT group (P < 0.05). The improved absolute maximum aerobic capacity and maximum breathing frequency were greatest in the RT group than in the NRT/RT, NRT, and Control groups. There was no significant difference between the changes in maximum heart rate. NRT/RT and RT groups had significantly greater improvements in 1-RM for chest press, leg press, and seated row as well as the composite RM as compared to the NRT group. The body mass index between the healthy cohort (HC) (23.17 ± 3.0) and smokers (25.05 ± 5.60) was not significantly different, neither was the height, weight, nor age. However, the body composition between these two groups was significantly different in all values analyzed. Total fat in the HC was 11.22 ± 10.97kg while smokers had a total fat of 18.06 ± 10.97kg. Trunk fat was measured at 4.69 ± 2.22kg in the HC and 7.90 ± 6.30kg in the smokers. There was a significant difference between body fat percentage with the smokers having and average of more than 5% higher than the HC and lean body mass was significantly lower for smokers as well.