Purpose: To assess periocular autologous fat transfer (AFT) survival by assessment of volume change with sequential 3D VECTRA imaging., Objective: Little is known about the patterns of graft survival of AFT in the periorbital region, especially in cases involving prior radiotherapy or trauma. The aim of this pilot study was to characterize fat survival following AFT in patients with a broad range of clinical indications, with and without a history of prior radiotherapy, for both periocular and orbital AFT, and in a subgroup of patients with an anophthalmic socket., Method: A single-institution, prospective cohort study involving 18 applications of AFT for volume augmentation in the periocular and orbital area. All patients had sequential 3D VECTRA photographs following a validated standardized protocol. Patient demographics, including gender, age, ethnicity, underlying diagnosis, and volume of fat injected, were also collected., Results: In total 13 patients were enrolled, 9 female (69.2%) and 4 male (31.0%). Mean age at the time of surgery was 47.8 years. Patients had volume deficiency secondary to a variety of causes; the most common cause was postenucleation socket syndrome following trauma in 6 patients (46.2%). The mean fat survival volume at the 1-month postoperative point was 70% and 55% by 6 months. AFT conducted with a multiport cannula for fat harvesting use had an initial higher rate of fat reabsorption with ANOVA p = 0.002, however, this was not observed at the later follow-up periods. There was no statistically significant difference in fat survival between abdominal or thigh donor fat sites. There was no statistically significant difference in residual injected volume at the early follow-up period between patients who had prior radiotherapy and those who did not p = 0.8496., Conclusion: AFT is an effective treatment for periorbital volume compromise with an acceptable survival rate in all categories of patients. Complex etiologies such as radiotherapy-related orbital and midface dysgenesis should not be a contraindication for AFT, with no difference in outcomes., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)