One in every five fatalities in the United States is caused by smoking, causing an estimated 480,000 deaths each year. While tobacco use is the leading preventable cause of mortality in the United States, the habit of tobacco use stems from the addictive nicotine content in cigarettes. Although the addictive and physiological health effects of tobacco have been broadly studied, the influence of personality on smoking motives has been relatively uninvestigated. The present study utilized psychometrically-sound measures of neuroticism and smoking motives in a sample of 77 daily chronic cigarette smokers, with the aim of characterizing the relationship between neuroticism and negative reinforcement smoking motives (e.g., smoking to alleviate anxiety or to reduce irritability). Our hypothesis that neuroticism score would be significantly, positively correlated with negative reinforcement motives was supported by a simple linear regression model. This model revealed that the slope of the simple linear regression line was statistically significant, suggesting that an increase in neuroticism score would be associated with an increase in negative reinforcement smoking motives, b = 0.037, t(84) = 2.45, p = 0.017. The model itself was also statistically significant, with neuroticism accounting for ~6% of the variance in negative reinforcement smoking motives score, R2 = 0.06, F(1,84) = 5.99, p = 0.016. Understanding the influence of personality dimensions on smoking motives has the potential to improve upon and inform new interventions for smoking cessation, potentially yielding increased success rates.