Background: Several personality traits have been linked to addictive behaviours, including smoking and excessive drinking. We hypothesised that the combination of low conscientiousness, high extraversion and high neuroticism would be synergistically associated with smoking, excessive drinking and both behaviours combined. Methods: Respondents aged 16+ years (N=363,454) were surveyed between 2009-2013 as part of the BBC Lab UK Study, with no restrictions on geographical location. Respondents provided information about sociodemographic characteristics, personality traits, and smoking and alcohol consumption. A series of multivariable logistic regression analyses were conducted. Results: No significant three-way but significant two-way interactive effects were observed. The association of high extraversion with smoking was more pronounced in those with high (vs. low) conscientiousness (OR_adj=1.51, 95% CI=1.46, 1.56, p<.001; OR_adj=1.38, 95% CI=1.35, 1.42, p<.001). The association of high extraversion with excessive drinking was more pronounced in those with low (vs. high) conscientiousness (OR_adj=1.70, 95% CI=1.67, 1.74, p<.001; OR_adj=1.60, 95% CI=1.56, 1.63, p<.001). The association of high extraversion with both behaviours combined was more pronounced in those with high (vs. low) conscientiousness (OR_adj=1.74, 95% CI=1.65, 1.83, p<.001; OR_adj=1.62, 95% CI= 1.56, 1.68, p<.001). Results remained largely robust in sensitivity analyses. Conclusions: In a large international survey, we identified two-way ‘personality typologies’ that are associated with greater odds of smoking, excessive drinking and both behaviours combined. The results may be useful for the tailoring of behaviour change interventions to at-risk individuals.