BACKGROUND: Inconsistent associations between modifiable risk factors and chronic back pain (CBP) may be due to the inability of traditional epidemiologic study designs to properly account for an array of potential genetic and environmental confounding factors. The co-twin control research design, comparing modifiable risk factors in twins discordant for CBP, offers a unique way to remove numerous confounding factors. PURPOSE: The study aimed to examine the association of modifiable lifestyle and psychological factors with lifetime CBP. STUDY DESIGN/SETTING: This is a cross-sectional co-twin control study in a nationwide sample of male twin members of the Vietnam Era Twin Registry. PATIENT SAMPLE: The sample is composed of 7,108 participants, including 1,308 monozygotic (MZ) pairs and 793 dizygotic pairs. OUTCOME MEASURE: The outcome measure is the self-reported lifetime history of CBP. METHODS: Lifestyle factors included body mass index (BMI), smoking history, alcohol consumption, habitual physical activity, and typical sleep duration. Psychological factors included depression (Patient Health Questionnaire-9) and posttraumatic stress disorder (PTSD) symptoms (PTSD Checklist). Covariates included age, race, education, and income. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated for the association of risk factors with lifetime CBP when considering twins as individuals, and a within-pair co-twin control analysis that accounted for familial and genetic factors. Funding was through VA Grant 5IK2RX001515; there were no study-specific conflicts of interest. RESULTS: The mean age of respondents was 62 years and the prevalence of lifetime CBP was 28%. All lifestyle factors were associated with CBP in the individual level analysis. However, none of these persisted in the within-pair analyses, except for severe obesity (BMI ≥35.0), which was associated with lifetime CBP in both individual-level (OR=1.6, 95% CI: 1.3-1.9) and within-pair analyses (MZ analysis: OR=3.7, 95% CI: 1.2-11.4). Symptoms of PTSD and depression were strongly associated with lifetime CBP in both the individual-level (moderate or severe depression: OR=4.2, 95% CI: 3.6-4.9, and severe PTSD: OR=4.8, 95% CI: 4.0-5.7) and within-pair (MZ) analyses (moderate or severe depression: OR=4.6, 95% CI: 2.4-8.7, and severe PTSD: OR=3.2, 95% CI: 1.6-6.5). CONCLUSIONS: Many associations between modifiable lifestyle risk factors and CBP are due to confounding by familial and genetic factors. Severe obesity, depression, and PTSD should be considered in the development of intervention strategies to reduce the prevalence of CBP.