Background: The existing literature suggests the presence of a possible relationship between high anger levels and smoking behavior; however, there are no available data highlighting possible differences between moderate and heavy smokers and the putative effect of gender on smoking behavior. Objectives: The aims of the current study were to assess the relationship among anger, depression, and anxiety and smoking patterns taking into account the possible mediator role of gender. Methods: 150 smokers and 50 nonsmokers volunteers were recruited from the staff of the University of Messina, Italy. The final sample consisted of 90 smokers, divided in 50 heavy smokers (HS: more than 40 cigarettes per day), 40 moderate smokers (MS: 10-30 cigarettes per day), and 42 nonsmokers (NS). All subjects were assessed by State-Trait Anger Expression Inventory-2, Self-Rating Depression Scale, and Self-Rating Anxiety Scale. Results: On anger, depression, and anxiety measures the HS group scored higher than MS and NS groups. HS showed higher than expected levels of trait-anger, a greater tendency to control anger reactions and to access to anger-management techniques. A moderate consumption of cigarettes (10-30 cigarettes per day) was not associated with negative emotions, as MS only showed higher than expected levels of state-anger. Cigarettes consumption was related to gender-specific anger features. Conclusions/Importance: Our study highlighted the importance of anger in smoking behavior and its related gender differences. Recognizing the link among anger, gender differences and smoking behavior could improve the knowledge for future-focused interventions on smoking cessation.