Brain microbleeds (MBs) are potential risk factors for future stroke, and hypertension is an established risk factor for MBs. However, data on other lifestyle-related risk factors and their joint effects with hypertension are limited. We enrolled 860 adults who underwent 1.5-T brain magnetic resonance imaging and had no history of stroke. Information on clinical risk factors was obtained from health-screening tests, and dietary history was assessed using a validated, brief, self-administered dietary questionnaire. Subjects were divided into three groups (no MBs, deep MBs and lobar MBs), which were compared for the potential risk factors; their joint effects with hypertension were assessed by logistic regression. Biologic interaction was estimated with the synergy index. After adjustment for possible confounders, age and systolic and diastolic blood pressures were found to be associated with the presence of MBs in a dose-dependent manner, especially in the case of deep MBs. With regard to lifestyle-related factors, current smoking status was significantly associated with deep MBs, and the odds ratio was 2.73 (95% confidence interval (CI) 1.15-6.48). We found that hypertension and current smoking status, higher alcohol consumption or lower calcium intake had joint effects on the risk of MBs and that hypertension and current smoking status had synergistic additive action (synergy index, 6.30; 95% CI 1.07-37.13). These results suggest that approaches combining lowering blood pressure and smoking cessation may greatly reduce the risk of MBs and contribute to preventing stroke.