Introduction: Platelets play a fundamental role in the pathogenesis of acute coronary syndrome (ACS). The platelet count (PC) at hospital admission is easy to obtain, but whether thrombocytopenia or/and thrombocytosis impact long-term mortality (LTM) after ACS is unclear. Objective: To evaluate the effect of PC at hospital admission on LTM in patients with ACS. Methods: This retrospective cohort study included patients with the ICD-10 codes for unstable angina (I.20) and acute myocardial infarction (I.21, I.22). Thrombocytopenia was defined as a blood PC <150 G/L and thrombocytosis as a PC >450 G/L. Additional platelet indices which were tested included plateletcrit (PCT), the mean platelet volume (MPV), the platelet distribution width (PDW), and the platelet larger cell ratio (P-LCR). Data on all-cause death were obtained from the National Health Fund database. Results: The study included 3,162 patients with a median follow-up of 27.2 months (interquartile range 12.5–46.8 months; max 68.7 months). Patients with thrombocytopenia and thrombocytosis yielded a higher maximal analyzed 5-year mortality rate in comparison with normal PC patients (45.8 and 47.7 vs. 24.2%, respectively; p < 0.00001) which was mainly driven by higher deaths at 1–2 years after ACS. The 5-year LTM was also significantly higher in patients with abnormal PCT and MPV levels in comparison with patients with PCT and MPV within the normal range. Other platelet indices (PDW, P-LCR) were not associated with a worse outcome. The Cox proportional hazards model revealed that thrombocytopenia at admission was independently associated with higher LTM after ACS (RR 1.83; 95% CI 1.1–3.0; p = 0.01). Conclusions: Both thrombocytopenia and thrombocytosis at hospital admission in post-ACS patients are associated with a significant almost two times higher 5-year mortality rate.