Introduction. The inflammatory response plays a potential role for the pathogenesis and adverse outcomes of heart failure (HF). We aimed to explore the predictive role of baseline neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume-to-lymphocyte ratio (MPVLR) on cardiovascular events (CVEs) in patients hospitalized with acute HF. Materials and Methods. A retrospective cohort study was conducted in 321 patients with HF between January 2017 and December 2019. The association between their NLR, MPVLR, and combined NLR and MPVLR and CVEs, rehospitalization for HF, in-hospital death, and a composite outcome was explored by survival analysis using a Cox proportional hazard model. They were separately investigated and compared with the area under the receiver operating characteristics curve (AUC). Results. Up to the end of the 3-year follow-up, 96 (29.9%) had CVEs, 106 (33.0%) died, 62 (19.3%) were rehospitalized with HF, and 21 (6.5%) died during admission. The NLR and MPVLR were significantly associated with CVEs (adjusted HR for
NLR
≥
3.29
, 3.11; 95% CI, 1.98-4.89;
MPVLR
≥
8.57
, 2.86; 95% CI, 1.87-4.39), readmissions for HF (adjusted HR for
NLR
≥
3.58
, 2.70; 95% CI, 1.58-4.61;
MPVLR
≥
6.43
, 2.84; 95% CI,1.59-5.07), in-hospital mortality (adjusted HR for
NLR
≥
3.29
, 9.54; 95% CI, 2.19-41.40;
MPVLR
≥
8.57
, 7.87; 95% CI, 2.56-24.19), and composite outcome (adjusted HR for
NLR
≥
3.32
, 4.76; 95% CI, 3.29-6.89;
MPVLR
≥
7.07
, 3.64; 95% CI, 2.58-5.15). The AUC of NLR and MPVLR for CVEs were 0.67 (95% CI, 0.61-0.72) and 0.63 (95% CI, 0.58-0.69). Combined NLR and MPVLR increased the AUC to 0.77 (95% CI, 0.72-0.83) with statistical significance. Conclusion. The elevated NLR and MPVLR on admission in patients with acute HF were independently associated with worse CVEs, rehospitalization for HF, in-hospital death, and composite outcomes. These economical biomarkers should be considered in the management and follow-up care of patients with acute HF.