Relatively few data have been reported on prospective changes in global longitudinal strain (GLS) following cardiac resynchronization therapy (CRT), and none are available on GLS during physical exercise. We investigated the effects of CRT on GLS, assessed by speckle tracking two-dimensional (2D) echocardiography, at rest and during exercise after a mid-term follow-up. Twenty consecutive CRT patients (45% ischaemic) were assessed prospectively by speckle tracking 2D echocardiography before implant (at rest) and at mid-term follow-up (during rest and bicycle exercise). GLS, septum and lateral wall longitudinal strain, left ventricular ejection fraction (LVEF), and conventional functional variables were evaluated at baseline and follow-up. All patients completed the study protocol at rest. Exercise images were available in 90% of the patients. At follow-up, GLS improved at rest from -7.1 ± 2.6% to -9.1 ± 4.5% (P