Introduction Left ventricular non-compaction (LVNC) is a rare cardiomyopathy with a progressive clinical course, resulting in symptoms such as heart failure, cardiac arrhythmias, or thrombo-embolic events. Little is known about the natural course of disease, in particular in individuals with normal LV ejection fraction (EF) at diagnosis. In this study, we aim to evaluate the outcome of this group of patients. Methods 48 LVNC patients with normal LV EF at diagnosis (defined as ≥50% by Simpson) were retrospectively analysed followed-up for median duration of 3656 days (2017–4965). All outcome data and conventional echocardiographic parameters were obtained; and in 27 patients, LV and right ventricular (RV) global longitudinal strain (GLS) were also determined using TomTec Image Arena (v.4.6). Results Mean age was 25.5 years. Median LVEF was 58.5% [IQR: 52.75 - 65.25]). The localization of non-compacted segments displayed a typical distribution with apical and inferolateral midventricular segments most frequently involved. Although LVEF was normal at baseline, median LV GLS was 16.8% (IQR: 20.0 - 14.2) and RV GLS was 18.7% (23.3–15.6). Furthermore, only 30 patients (73.2%) had a normal diastolic function, while others showed impaired relaxation (19.5%; n=8) or restrictive filling pattern (7.3%; n=3). During follow-up, LVEF decreased slightly from the initial visit (59%, [53.3–65.0]) to last follow-up (56%, [53.0–61.8], p=0.0009), and LV end-systolic and end-diastolic volumes increased (p=0.009 and 0.001, respectively). The other echocardiographic parameters did not show any significant changes. During follow-up, 3 patients (7.7%) died, 5 (12.8%) were hospitalized for heart failure, 3 (7.7%) had a thromboembolic event, 5 (12.8%) a syncope, 3 (8.1%) a non-sustained ventricular tachycardia, 9 (22.5%) a supraventricular tachycardia, and 14 (35.9%) suffered other complications during follow-up. The change in LVEF and LV volumes during follow-up was not significantly associated with outcome. Conclusion Patients presenting with a LVNC phenotype and normal LVEF did not display a completely normal LV function as revealed by LV strain and LV diastolic function. LVEF decreased slightly during follow-up, but was surprisingly stable in most patients. Nevertheless, a significant number of individuals experienced a clinically relevant event. Hence, a LVNC phenotype is important even in individuals with normal LVEF and such patients should be followed-up regularly.