Despite the recent advanced developments in radiation therapy planning, treatment planning for head-neck and pelvic cancers remains challenging due to large concave target volumes, multiple dose prescriptions and numerous organs at risk close to targets. Inter-institutional studies highlighted that plan quality strongly depends on planner experience and skills. Automated optimization of planning procedure may improve plan quality and best practice. We performed a comprehensive dosimetric and clinical evaluation of the Pinnacle3 AutoPlanning engine, comparing automatically generated plans (AP) with the historically clinically accepted manually-generated ones (MP). Thirty-six patients (12 for each of the following anatomical sites: head-neck, high-risk prostate and endometrial cancer) were re-planned with the AutoPlanning engine. Planning and optimization workflow was developed to automatically generate “dual-arc” VMAT plans with simultaneously integrated boost. Various dose and dose-volume parameters were used to build three metrics able to supply a global Plan Quality Index evaluation in terms of dose conformity indexes, targets coverage and sparing of critical organs. All plans were scored in a blinded clinical evaluation by two senior radiation oncologists. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Autoplanning was able to produce high-quality clinically acceptable plans in all cases. The main benefit of Autoplanning strategy was the improvement of overall treatment quality due to significant increased dose conformity and reduction of integral dose by 6–10%, keeping similar targets coverage. Overall planning time was reduced to 60–80 minutes, about a third of time needed for manual planning. In 94% of clinical evaluations, the AP plans scored equal or better to MP plans. Despite the increased fluence modulation, dose measurements reported an optimal agreement with dose calculations with a γ-pass-rate greater than 95% for 3%(global)-2 mm criteria. Autoplanning engine is an effective device enabling the generation of VMAT high quality treatment plans according to institutional specific planning protocols.