||BACKGROUND: Individuals experiencing chronic widespread pain (CWP) have greater disability and poorer quality of life compared to those with other chronic painful conditions; although research identifying risk factors for CWP is lacking. We aimed to investigate whether parental CWP increases the risk of offspring CWP, and if offspring body mass index (BMI) and leisure time physical activity modify this association. METHODS: We included 6589 parent-offspring trios participating in the Norwegian HUNT Study in 1995-1997 and 2006-2008. Logistic regression was used to calculate adjusted odd ratios (ORs) (95% confidence intervals, CIs) as estimates of relative risk for offspring CWP. We analysed the joint effect of parental CWP and offspring BMI or leisure time physical activity on offspring risk of CWP and calculated the relative excess risk due to interaction (RERI). RESULTS: In total, 886 (13.5%) offspring developed CWP during follow-up. Having one (OR = 1.23, 95% CI, 1.05-1.44) or both parents with CWP (OR = 1.89, 95% CI, 1.50-2.38) increased the risk of offspring CWP. In analyses of joint effects, ORs were 1.84 (95% CI, 1.31-2.56) and 3.35 (95% CI, 1.94-5.77) in normal weight and obese offspring, respectively, when both parents had CWP. The estimate of RERI suggested some synergistic effect (RERI = 1.19, 95% CI, -0.68 to 3.05), although precision was low. Risk of CWP was similar in active (OR = 2.05, 95% CI, 1.56-2.70) and inactive (OR = 1.96, 95% CI, 1.31-2.91) offspring when both parents had CWP. CONCLUSION: Parental CWP increases the risk of CWP in adult offspring, particularly if both parents have CWP and offspring are obese. This highlights a familial predisposition for CWP and an important target group for preventive measures. SIGNIFICANCE: The parent-offspring transmission of CWP is stronger in obese offspring (particularly when both parents have CWP). This study is the first to investigate the interaction between modifiable lifestyle factors, familial factors and CWP.