This study describes a method for setup optimization in patient simulation for ocular proton therapy (OPT) at the National Center for Oncological Hadrontherapy (CNAO) in Pavia, Italy, with the aim of minimizing the occupancy time of clinical areas and streamlining the actual procedure. Setup repeatability is ensured by patient-specific immobilization tools and relies on the patient’s ability to maintain a stable gaze direction according to the treatment plan. This is facilitated by aligning a light source (LED) on a patient-specific base along the prescribed gaze direction. At CNAO, a dedicated Eye-Tracking System (ETS) was designed to provide the patient with a visible source of light aligned to the desired gaze direction. The ETS position is defined prior to treatment planning, relying on optical-tracking guidance and comparing the position of passive markers fixed on the ETS chassis with patient-specific models prepared offline in accordance with the desired geometry. OPT at CNAO started in 2016 and may be considered as a consolidated clinical routine. However, all the preparation phases, including patient-specific ETS models and setup, still require long sessions in clinical areas such as the computed tomography (CT) and the treatment rooms, with a non-negligible impact on other activities. This study describes a novel approach for patient-specific definition of the ETS position and orientation, aiming at minimizing the time required for preparatory activities inside clinical areas. To minimize the occurrence of biases and to reproduce as much as possible a real end-to-end approach, we included in the analysis data of patients that received OPT in our facility. The study was performed in parallel, carrying out the alignment with the standard method currently used in the clinical workflow of CNAO and with the proposed method. Results are presented as 3D residuals and gaze deviations, comparing ETS alignment based on the new approach with respect to the clinical standard method. The preliminary results of this study are evidence of the capability of the procedure to align the ETS position, allowing performing of the procedure in a non-clinical dedicated room.