High-virulence Helicobacter pylori strains and smoking increase the risk of gastric precancerous lesions. However, its association with specific types of intestinal metaplasia has been poorly studied. We aimed to quantify the association between different types of intestinal metaplasia (complete, incomplete, and mixed) and these two risk factors. Male volunteers (n = 227) underwent an upper digestive endoscopy and completed symptoms and lifestyle questionnaires. A histologic diagnosis was assigned based on the lesions found in any of the biopsy specimens (antrum, body, or incisura). H. pylori vacA and cagA were directly genotyped by multiplex PCR and reverse hybridization. Each participant's smoking status at the time of endoscopy was assessed. Logistic and multinomial logistic regression models were fitted (including H. pylori virulence, smoking, age, and education as independent variables) using normal/chronic nonatrophic gastritis as the reference category. Compared with never smokers infected with low-virulence strains, the risk of intestinal metaplasia was increased in subjects infected with high-virulence strains [odds ratio (OR), 5.74; 95% confidence interval (95% CI), 1.68-19.63] and in ever smokers (OR, 3.54; 95% CI, 1.30-9.61). In ever smokers infected with high-virulence H. pylori strains, the risk of intestinal metaplasia was further increased (OR, 8.61; 95% CI, 3.07-24.17). Infection with high-virulence strains significantly increased the risk of incomplete (OR, 9.81; 95% CI, 2.39-40.31) and mixed (OR, 3.28; 95% CI, 1.51-7.14) intestinal metaplasia. Complete (OR, 2.82; 95% CI, 1.01-7.88) and mixed (OR, 2.97; 95% CI, 1.12-7.84) intestinal metaplasia were more frequent among ever smokers. High-virulence H. pylori strains and smoking are differentially associated with the complete and incomplete types of intestinal metaplasia, suggesting divergent pathways in gastric carcinogenesis.