Objective <p>A substantial body of evidence suggests that oral health, particularly periodontitis, is closely linked to overall systemic well-being. This systematic review and meta-analysis evaluate the specific relationship between this chronic inflammatory oral condition and the onset of new cardiovascular events. Method: Adhering to PRISMA guidelines, a thorough literature search of major databases from 2000 to 2024 was performed to identify relevant cohort studies involving adults free from pre-existing cardiovascular disease. The methodological rigor of the included studies was appraised using the ROBINS-E tool. The main pooled estimate included all 30 qualifying cohort studies and is therefore reported as a broader periodontal/oral health-related exposure analysis. Restricted sensitivity analyses were conducted for clinically diagnosed or periodontitis-coded exposure and for confirmed major cardiovascular outcomes. Results: The analysis found that periodontal/oral health-related exposure was associated with a 31% elevated risk of developing cardiovascular disease (HR = 1.31, 95% CI: 1.13–1.48). The link was most potent for stroke and demonstrated a dose-response pattern, where greater disease severity correlated with higher risk. Interventions like periodontal treatment were correlated with a decrease in risk. Significant heterogeneity was noted, largely due to variations in study design. Conclusion: In conclusion, the broader periodontal/oral health-related analysis showed a 31% elevated risk for cardiovascular disease, although substantial heterogeneity limits the interpretability of this estimate. Nevertheless, the findings underscore the importance of oral health management in comprehensive cardiovascular risk mitigation strategies.</p> PROSPERO <p>Registration in the PROSPERO database was done before initiating the investigation [CRD420251173688].</p>