Cardiovascular diseases (CVD) remain a leading cause of global mortality, with atherosclerosis and inflammation playing pivotal roles in their development. The neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-HDL cholesterol ratio (NHR) have emerged as potential biomarkers for assessing CVD risk. In this community-based cohort study conducted in Taiwan, involving 3278 participants, we investigated the associations between NHR, NLR, and the risks of CVD and all-cause mortality. Our findings revealed that both NHR and NLR were effective in identifying individuals at high risk for CVD. However, when assessing their joint effect, NHR alone demonstrated a stronger predictive value for CVD prognosis than NLR or the combination of both markers. Furthermore, NLR alone showed potential as a predictor of all-cause mortality when compared with NHR alone or in combination with NLR and NHR. These findings underscore the complex interplay between inflammation and lipid metabolism in the pathogenesis of CVD. While NHR shows promise as a cost-effective tool for CVD risk assessment, NLR emerges potential as a prognostic marker for mortality. Further research is warranted to explore the dynamic changes in these markers and their implications for clinical practice.