This study investigates the relationship of neutrophil-lymphocyte ratio (NLR) with the risk of all-cause and cardiovascular mortality in patients with cardiovascular disease. The data for this analysis came from 2239 participants with cardiovascular disease of the National Health and Nutrition Examination Survey conducted between 1999-2018. The optimal cutoff point for NLR was determined using maximally selected rank statistics. Survival analysis was performed using Cox regression models to assess the impact of NLR on the risk of all-cause mortality and cardiovascular mortality. Restricted cubic spline was used to visualize the association of NLR with mortality risk. Subgroup analysis was performed to examine the relationship between NLR and mortality within subgroups based on age, sex, diabetes and hypertension. During a median follow-up period of 6.7 (IQR, 3.3-10.9) years, 992 all-cause deaths occurred, including 381 cardiovascular deaths. Our study revealed that NLR is a risk factor for all-cause mortality (HR: 1.15 95%Cl: 1.11 ~ 1.19) and cardiovascular mortality (HR: 1.14 95%Cl: 1.08 ~ 1.2) among patients with cardiovascular disease. The restricted cubic spline regression analysis showed a non-linear association between NLR and all-cause mortality (p < 0.05 for nonlinearity) in cardiovascular patients. This association remained robust in subgroup analyses stratified by age, sex, diabetes, and hypertension. Conclusion NLR stands as a significant risk factor for both all-cause and cardiovascular mortality among patients with cardiovascular disease.