Purpose: The purpose of this pilot study was to assess feasibility, safety, and accuracy of detection of metastatic nodes intraoperatively with a hand-held gamma (PET) probe after administration of ¹⁸F-FDG in patients with high risk endometrial cancer (EC). Materials and Methods: This is a prospective, cohort study. Twenty-two patients with clinical Stage I or II EC with high-risk histologic subtypes who were candidates for open surgical intervention were screened for the study. After screening, there were seven study patients (mean age: 64; range: 53-77) who were eligible for the study. In the entire cohort, there were 61 nodal stations that were assessed with a gamma counter intraoperatively, in vivo and again after removal of the node. All adverse events were recorded and operating room staff was monitored for radiation exposure. Resected nodes underwent histological assessment as per routine clinical practice. Results: Range of maximal counts per second recorded in vivo and ex vivo were 0-86 and 0-17, respectively. Of all the nodes examined, one node was positive for metastatic disease; however, intraoperatively the lymph node readings were not higher than other lymph node basins assessed in same patient. No adverse events were recorded. The surgeons recorded the maximum average radiation exposure of all healthcare personnel with an average exposure of 0.08 mSV per case (range, 0.06-0.15). Conclusion: Use of hand-held gamma probe for intraoperative staging of patients with high risk EC is feasible, safe, and radiation exposure levels for all members of the healthcare team were within radiation safety guidelines. However, its use for detection of lymph node metastases needs further evaluation.