Aims Cardiac resynchronization therapy (CRT) involves time-consuming procedures to achieve an optimal programming of the system, at implant as well as during follow-up, when remodelling occurs. A device equipped with an implantable sensor able to measure peak endocardial acceleration (PEA) has been recently developed to monitor cardiac function and to guide CRT programming. During scanning of the atrioventricular delay (AVD), PEA reflects both left ventricle (LV) contractility (LV dP/dtmax) and transmitral flow. A new CRT optimization algorithm, based on recording of PEA (PEAarea method) was developed, and compared with measurements of LV dP/dtmax, to identify an optimal CRT configuration. Methods and results We studied 15 patients in New York Heart Association classes II–IV and with a QRS duration >130 ms, who had undergone implantation of a biventricular (BiV) pulse generator connected to a right ventricular (RV) PEA sensor. At a mean of 39 ± 15 days after implantation of the CRT system, the patients underwent cardiac catheterization. During single-chamber LV or during BiV stimulation, with initial RV or LV stimulation, and at settings of interventricular intervals between 0 and 40 ms, the AVD was scanned between 60 and 220 ms, while LV dP/dtmax and PEA were measured. The area of PEA curve (PEAarea method) was estimated as the average of PEA values measured during AVD scanning. A ≥10% increase in LV dP/dtmax was observed in 12 of 15 patients (80%), who were classified as responders to CRT. In nine of 12 responders (75%), the optimal pacing configuration identified by the PEAarea method was associated with the greatest LV dP/dtmax. Conclusion The concordance of the PEAarea method with measurements of LV dP/dtmax suggests that this new, operator-independent algorithm is a reliable means of CRT optimization.