Background: Pre-infarction angina reduces myocardial infarct size by preventing the myocardium from being subjected to ischemia reperfusion (I/R) injury. Ischemic preconditioning is the proposed mechanism for this effect. Sphingosine 1 phosphate (S1P) activates ischemic preconditioning pathways and may play a role in the presence of cardioprotective effects of pre-infarction angina. Therefore, we evaluated the relationship between pre-infarction angina and serum S1P levels. Methods: Between May 2011 and January 2012, 79 patients with acutemyocardial infarction were included in the study. In addition to taking routine medical histories, all of the patients were questioned as to whether or not they had pre-infarction angina. We determined patients serum levels of S1P at admission and discharge, and peak creatine kinaseMBand troponin levelswere alsomeasured in the pre-infarction angina positive and negative groups. Results: Of the 79 patients included in the study, 36 had pre-infarction angina and 43 had not. Baseline characteristics were similar between the groups. The median level of serum S1P in patients with pre-infarction angina was significantly higher than in those without pre-infarction angina both at admission and discharge [0.54 (0.14-1.35) vs. 0.26 (0.12-0.62) p = 0.014/0.51 (0.20-1.81) vs. 0.30 (0.13-0.68) p = 0.010]. Serum high sensitive troponin levels were significantly lower in patients with pre-infarction angina [0.97 (0.39-3.07) vs. 2.56 (0.9-6.51) p = 0.034]. Serum S1P levels both at admission and discharge tended to be higher in patients with more angina episodes, but the differences between these subgroups were not statistically significant. Conclusions: Patients who experienced pre-infarction angina had higher serum S1P levels than patients without pre-infarction angina. This study supported our hypothesis that the cardioprotective effects of pre-infarction angina may in part be mediated by S1P.