Mammographic density (MD), or the proportion of the breast with respect to its overall area that is composed of dense tissue, is a strong risk factor for breast cancer. Studies support a positive association of mammographic density and alcohol drinking. This was a cross-sectional multicenter study based on 3584 women, aged 45-68 years, recruited from seven screening centers within the Spanish breast cancer screening program network. The association between MD, alcohol consumption and tobacco use was evaluated by using ordinal logistic models with random center-specific intercepts. We found a weak positive association between current alcohol intake and higher MD, with current alcohol consumption increasing the odds of high MD by 13% (OR = 1.13; 95% CI 0.99-1.28) and high daily grams of alcohol being positively associated with increased MD (P for trend = 0.045). There were no statistically significant differences in MD between smokers and non-smokers. Nevertheless, increased number of daily cigarettes and increased number of accumulated lifetime cigarettes were negatively associated with high MD (P for trend 0.017 and 0.021). The effect of alcohol on MD was modified by menopausal status and tobacco smoking: whereas, alcohol consumption and daily grams of alcohol were positively associated with higher MD in postmenopausal women and in women who were not currently smoking, alcohol consumption had no effect on MD in premenopausal women and current smokers. Our results support an association between recent alcohol consumption and high MD, characterized by a modest increase in risk at low levels of current consumption and a decrease in risk among heavier drinkers. Our study also shows how the effects of alcohol in the breast can be modified by other factors, such as smoking.