UNLABELLED: Chronic pain is common during adolescence and young adulthood and is associated with poor quality of life, depression, and functional disability. Recognizing that chronic pain has significant consequences, it is important to identify modifiable health behaviors that may place young adults at risk for chronic pain. This study examines associations between chronic musculoskeletal pain and smoking in young adult twins (n = 1,588, ages 18-30) participating in a statewide twin registry. Twins completed questionnaires assessing smoking, mood (anxiety, depressive symptoms, and stress), and chronic musculoskeletal pain. Analyses examined associations between chronic pain and smoking, particularly the role of genetics/shared familial factors and psychological symptoms. As predicted, results revealed a near-2-fold increased risk for chronic musculoskeletal pain in twins who currently smoked compared to nonsmokers, even when accounting for psychological factors. Results of within-pair analyses were only minimally attenuated, suggesting that associations between smoking and chronic musculoskeletal pain are better accounted for by nonshared factors than by shared familial factors/genetic effects. Future twin research is needed to identify what nonshared factors (eg, attitudes, direct effects of smoking on pain) contribute to these associations to further understand comorbidity. Longitudinal studies and recruitment of participants prior to smoking initiation and chronic pain onset will better identify causal associations. PERSPECTIVE: This article describes associations between musculoskeletal pain and smoking in young adult twins, taking into account psychological symptoms. Findings highlight the importance of nonshared factors in associations between pain and smoking and the need to explore the roles of lifestyle, individual attitudes, and direct effects of smoking on pain.