BackgroundCardiac resynchronization therapy (CRT) is indicated in symptomatic heart failure (HF) patients after achieving optimal medical therapy (OMT). However, many patients may not be under OMT when the CRT device is implanted. Here, we evaluate the long‐term benefits of CRT in symptomatic HF patients receiving or not OMT.MethodsWe investigated the effect of OMT on HF developing or death in 328 consecutive patients with a CRT device implanted between 2005 and 2015 in a single tertiary center. After the CRT implant, we categorized the patients into three groups: no OMT, OMT at baseline and after 1 year of follow‐up, and OMT only at the 1‐year follow‐up but not at baseline. We used multivariate Cox proportional hazards model to determine the effect of OMT on clinical outcomes.ResultsOne hundred and twenty‐two patients (37.2%) received OMT prior to CRT. OMT at baseline was not associated with a reduced risk of death or HF (HR 0.72; 95% CI 0.50‐1.02; P = 0.067) compared with no‐basal‐OMT patients. After CRT, patients without OMT had a higher risk of death or HF than patients who received OMT in follow‐up (HR 1.72, 95% CI 1.07‐2.78, P = 0.025), and the risk of the patients who received OMT at baseline and at the 1‐year follow‐up was similar to that of the patients who achieved OMT at the 1‐year follow‐up (HR 0.90, 95% CI 0.54‐1.50, P = 0.682).ConclusionBasal OMT prior to CRT is not associated with better outcomes in terms of HF/death compared with no basal OMT. The subgroup of patients who achieved OMT at the 1‐year follow‐up exhibited a reduced risk of HF and death compared with patients who did not.