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Cardiac resynchronization therapy (CRT) is currently limited to those with left ventricular ejection fraction (LVEF) ≤35%. To evaluate whether patients with LVEF >35% might benefit from CRT, we performed a retrospective analysis of the predictors of response to CRT (PROSPECT) database.PROSPECT was a prospective, multicentre study that enrolled CRT patients based on enrolling centre-evaluated LVEF <35%, but all echocardiograms were subsequently analysed by a core laboratory. Patients with core laboratory-measured LVEF >35% (OVER35) were compared with those whose LVEF was <35% (UNDER35). Clinical composite score (CCS) and change in LV end systolic volume (LVESV) were analysed from baseline to 6-month follow-up. Of 361 patients, 86 (24%) had LVEF >35%. At entry, OVER35 had smaller LV volumes, shorter QRS duration, shorter 6-min walk distance, and were more likely to have ischaemic aetiology than UNDER35. Outcomes were comparable between the groups, with 62.8% of OVER35 improved in CCS (70.2% in UNDER35) and 50.8% of OVER35 improved in LVESV (57.8% in UNDER35).Patients with LVEF >35%, New York heart association functional Class III–IV status, and QRS >130 ms appear to derive clinical and structural benefit from CRT. As CRT may offer a valuable option for these patients, this hypothesis should be formally tested in a prospective, randomized multicentre trial.