BackgroundWhen frozen pathological results of suspicious peritoneal nodules found in gastric cancer (GC) patients are negative or indeterminant, whether to perform gastrectomy will always be a dilemma for surgeons. This study aimed to facilitate intraoperative surgical decision-making based on frozen section (FS) results and clinicopathological characteristics. MethodsFrom January 2015 to July 2021, 318 GC patients were enrolled retrospectively. The correlations between frozen and paraffin pathology of peritoneal nodules were examined. Then, predictive factors of positive paraffin section (PS) results were identified, and a nomogram was constructed. The survival significance of gastrectomy was also explored. ResultsOf 70 FS-negative patients, 59 (84.3%) had concordant negative PS results, while the PS results of 11 (15.7%) were positive. Forty-six (93.9%) and 3 (6.1%) of 49 patients with indeterminant FS results had positive and negative PS results, respectively. The PS results of 95 FS-positive patients were all positive. A nomogram for predicting positive PS results was developed based on Lauren type, nodule distribution, and CA125. Gastrectomy for FS-negative patients improved survival compared to no gastrectomy (HR 0.26, 95% CI 0.11–0.62; P = 0.0012). Survival benefits for gastrectomy vs. no gastrectomy were not demonstrated in patients with indeterminant (HR 0.74, 95% CI 0.27–2.01; P = 0.53) and positive (HR 0.87, 95% CI 0.43–1.74; P = 0.69) FS results. ConclusionsGastrectomy can be justified for the treatment of operable GC patients with negative frozen pathological results of peritoneal nodules. For patients with positive and indeterminant frozen pathological results, gastrectomy is not recommended unless it is performed as palliative surgery.