Introduction: Research suggests that physical activity protects against youth smoking. As a result, prevention programs that focus on physical activity to address the problem of smoking hold promise. However, more research is needed to examine the relationship between physical activity and smoking and how physical activity might be used in smoking prevention and intervention programs. The present study examined the relationship between physical activity and smoking among adolescents and young adults using a sample from Cyprus. We investigated the association between level of physical activity (very active, active, moderately active, or inactive) and type of smoking behavior (nonsmoker; occasional, regular light, or regular heavy smoker). Methods: Participants were 1,390 Cypriot adolescents and young adults who completed a packet of questionnaires related to smoking and physical activity. Physical activity and demographic factors were analyzed in terms of their effect on smoking behavior. Results: A consistent and negative relationship between physical activity and smoking emerged across both sex and age. The greater the intensity of youths' physical activity, the less likely they were to smoke. Compared with inactive individuals, physically active individuals smoked fewer cigarettes and were more likely to be nonsmokers or occasional smokers. Among physically active individuals, those engaging in more intense activity were less likely to be heavy or light smokers. Discussion: Results of the present study indicate that physical activity may be used as a preventive measure against smoking in adolescents and young adults.