Myocardial strain is a well validated parameter for estimating left ventricular (LV) performance. The aim of our study was to evaluate the inter-study as well as intra- and interobserver reproducibility of fast-SENC derived myocardial strain. Eighteen subjects (11 healthy individuals and 7 patients with heart failure) underwent a cardiac MRI examination including fast-SENC acquisition for evaluating left ventricular global longitudinal (GLS) and circumferential strain (GCS) as well as left ventricular ejection fraction (LVEF). The examination was repeated after 63 [range 49‒87] days and analyzed by two experienced observers. Ten datasets were repeatedly assessed after 1 month by the same observer to test intraobserver variability. The reproducibility was measured using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Patients with heart failure demonstrated reduced GLS and GCS compared to healthy controls (-15.7 ± 3.7 vs. -20.1 ± 1.4; p = 0.002 for GLS and -15.3 ± 3.7 vs. -21.4 ± 1.1; p = 0.001 for GCS). The test-retest analysis showed excellent ICC for LVEF (0.92), GLS (0.94) and GCS (0.95). GLS exhibited excellent ICC (0.99) in both intra- and interobserver variability analysis with very narrow limits of agreement (-0.6 to 0.5 for intraobserver and -1.3 to 0.96 for interobserver agreement). Similarly, GCS showed excellent ICC (0.99) in both variability analyses with narrow limits of agreement (-1.1 to 1.2 for intraobserver and -1.7 to 1.3 for interobserver agreement), whereas LVEF showed larger limits of agreement (-14.4 to 10.1). The analysis of fast-SENC derived myocardial strain using cardiac MRI provides a highly reproducible method for assessing LV functional performance.