Purpose To assess the efficacy of an instrument-integrated OCT (iiOCT)-based distance sensor during robotic vitreoretinal surgery using the Preceyes Surgical System (PSS; Preceyes B.V.). Design Single-center interventional study. Participants Patients requiring vitreoretinal surgery. Methods Five patients were enrolled. Standard preoperative OCT images were obtained. After vitrectomy, a predefined set of actions was performed using the iiOCT-based sensor. Images then were processed to assess the signal-to-noise ratio (SNR) at various angles to the retina and at different distances between the instrument tip and the retinal surface. Preoperative and intraoperative OCT images were compared qualitatively and quantitatively. Main Outcomes Measures The feasibility in performing surgical tasks using the iiOCT-based sensor during vitreoretinal surgery, the SNR when imaging the retina, differences among intraoperative and preoperative OCT images, and characteristics of intraoperative retinal movements detected with the iiOCT-based probe. Results Surgeons were able to perform all the tasks but one. The PSS was able to maintain a fixed distance. The SNR of the iiOCT-based sensor signal was adequate to determine the distance to the retina and to control the PSS. Analysis of iiOCT-based sensor A-scans identified 3 clearly distinguishable retinal layers, including the inner retinal boundary and the interface at the retinal pigment epithelium–Bruch’s membrane. Thickness values differed by less than 5% from that measured by preoperative OCT, indicating its accuracy. The Fourier analysis of iiOCT-based sensor recordings identified anteroposterior retinal movements attributed to heartbeat and respiration. Conclusions This iiOCT-based sensor was tested successfully and promises reliable use during robot-assisted surgery. An iiOCT-based sensor is a promising step toward OCT-guided robotic retinal surgery.