Introduction: Drinking behavior differs not only among countries, but also among regions within a country. However, the extent of such variation and the interplay between gender and regional differences in drinking have not been explored and are addressed in this study. Methods: Data stem from 105,061 individuals from 23 countries of the GENACIS data set. The outcomes were heavy drinking (10/20 g or more of pure ethanol per day for women/men), and risky single occasion drinking (RSOD) (5+ drinks per occasion) at least monthly. Analyses used binary logistic mixed models. Variance at specific levels was measured by the intra-class correlation coefficient (ICC). Gender differences in outcomes were measured using gender ratios. Results: Country-level ICC was 0.13 (95% CI: 0.09-0.18) for heavy drinking and 0.16 (95% CI: 0.10-0.26) for RSOD. Within-country regional-level ICC for heavy drinking and RSOD was 0.02 (95% CI: 0.009-0.05; 0.01-0.04, respectively), implying that 2% of variation in heavy drinking and RSOD was explained by regional variation. Variance in drinking indicators was larger for women compared to men across countries. Gender ratios were higher in low- and middle-income countries. Conclusions: Regional variations in risky drinking were more often present in low- to middle-income countries as well as in a few higher-income countries, and could be due to cultural and demographic differences. Variations in gender differences were larger on the country level than on the regional level, with lower-income countries showing larger differences. These results can help to better identify specific high-risk groups for prevention strategies.