OBJECTIVES: This nested cross-sectional study of dyadic sexual encounters with new male partners reported by men living in England who have sex with men tested moderation between drug use and location of sex in associations with unprotected anal intercourse (UAI). METHODS: Data were drawn from two waves of a longitudinal monthly internet survey of men living in England who have sex with men conducted in 2011. Using generalised estimating equations and logit link, we tested the relationship with UAI of any respondent drug use before sex, specific respondent drug use before sex, location of sex (distinguishing private, sex-on-premises venue and cruising locations) and location-drug use interactions. RESULTS: Any respondent drug use (OR 1.57, 95% CI 1.31 to 1.88) was associated with increased odds of UAI. Relative to encounters in private locations, encounters in sex-on-premises venues (0.69, 95% CI 0.52 to 0.91), but not cruising locations, were associated with decreased odds of UAI. Any respondent drug use, respondent use of poppers and respondent use of alcohol were each associated with increased UAI in sex-on-premises venues. DISCUSSION: This analysis presents evidence of moderation between drug use and location of sex in associations with UAI. Though this analysis used a large sample, it relied on community-recruited respondents. Our findings may reflect either 'totalising' effects of drug use across venues or site-specific use of drugs as a mechanism for cognitive escape. Additional qualitative research is necessary to understand these findings in context.