Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of layer-specific GLS has not yet been investigated in patients with suspected stable angina pectoris (SAP). We sought to investigate the prognostic value of layer-specific and whole wall GLS in patients with suspected SAP. From September 2008 to March 2011, 296 consecutive patients with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were enrolled in a prospective cohort study. Patients underwent echocardiography including two-dimensional speckle tracking at rest, exercise stress test, and coronary angiography. The end-point was a composite of incident heart failure, acute myocardial infarction, and cardiovascular death (MACE). Out of the 285 included patients (mean age 61 years, 50% male), 24 (8%) developed MACE during a median follow-up of 3.5 years. Both endocardial [hazard ratio (HR) 1.21, 95% CI 1.08–1.35, p = 0.001], epicardial (HR 1.29, 95% CI 1.12–1.50, p = 0.001) and whole wall GLS (HR 1.25, 1.10–1.42, p = 0.001) were significantly associated with an increased risk of developing MACE during follow-up in univariable Cox regression analysis. In multivariable analysis, only epicardial (HR 1.23, 95% CI 1.00–1.51, p = 0.046) and whole wall GLS (HR 1.20, 95% CI 1.00–1.43, p = 0.049) remained significantly associated with an increased risk of MACE independent of various baseline clinical variables, left ventricular ejection fraction (LVEF), E/eʹ and Duke Score. Layer-specific and whole wall GLS were significant predictors of MACE in this cohort of patients with suspected SAP independent of various baseline clinical variables, LVEF, E/eʹ and Duke Score.