Prior studies demonstrated the association between the major adverse cardiovascular outcomes and both higher platelet and lower lymphocyte counts. Our study explores the value of the platelet/lymphocyte ratio (PLR) as a marker of long-term mortality in patients presented with non-ST segment elevation myocardial infarction (NSTEMI). This is an observational study with a total 619 NSTEMI patients admitted to a tertiary center between 2004 and 2006. Patients were stratified into equal tertiles according to their admission PLR. The primary outcome, 4 year all-cause mortality, was compared among the PLR tertiles. The first, second and third PLR tertiles were PLR < 118.4, 118.4 ≤ PLR ≤ 176, and PLR > 176, respectively) included 206, 206 and 207 patients, respectively. There was a significant higher 4 year all-cause mortality in the higher PLR tertiles (the mortalities were 17, 23 and 42 % for the first, second and third PLR tertiles respectively, p < 0.0001). After exclusion of patients expired in the first 30 days, patients in the first PLR tertile had a significant lower 4 year mortality (33/205, 16 %) versus those in the third PLR tertile (72/192, 38 %), p < 0.0001. After controlling for Global Registry of Acute Coronary Events risk scores and other confounders, the hazard ratio of mortality increased 2 % per each 10 U increase of PLR (95 % CI 1.01-1.03, p < 0.0001). In patients with PLR ≥ 176, the mortality rate was statistically higher in those received mono-antiplatelet (30/60 = 50 %) compared to those received dual antiplatelet therapy (48/149 = 32 %), p = 0.0018. However in PLR < 176, the mortality was not significantly different between mono-antiplatelet group (20/94 = 21 %) versus dual antiplatelets group (53/213 = 25 %), p = 0.56. The PLR is a significant independent predictor of long-term mortality after NSTEMI. Among patients with PLR > 176, patients with dual antiplatelet therapy had lower mortality versus those with mono-platelet therapy. Further studies are needed to clarify these findings.