In humans, thrombocytopenic patients have increased incidence of post-hepatectomy liver failure (PHLF), but existing evidence is heterogeneous. Our objective was to determine if preoperative platelet count or antiplatelet drugs were associated with PHLF.Patients who underwent hepatic resection in the University Hospitals of Geneva, Switzerland, from 01.12.2009 to 18.12.2018 were identified. Platelet count at day 0, postoperative days (POD) 1, 3, and 5 were retrieved. Occurrence of PHLF according to the ISGLS definition was determined. Logistic regression was performed to determine if platelet count or antiplatelet drug were predictors for PHLF.Five hundred ninety seven patients were included. Eighty patients (17.8%) had a preoperative platelet count <150 (G/l) and 24 patients (5.3%) had a platelet count <100 (G/l). Thirty five patients (5.9%) were under antiplatelet drug. Platelet count significantly decreased at POD 1 and POD 3 when compared to preoperative platelet count (182 ± 71.61 (G/l) vs 212 ± 85.26 (G/l), P < .0001; 162 ± 68.5 (G/l) vs 212 ± 85.26 (G/l), P < .0001). At POD 5, post-operative platelet count did not significantly differ from its preoperative value. Forty three patients (11.2%) suffered from PHLF. Their platelet count was not significantly different than patients without PHLF (211 ± 89.7 (G/l) vs 211 ± 83.5 (G/l), P = .671). One patient with PHLF had a platelet count <100 (G/l) and 5 had a count <150 (G/l). Univariate logistic regression did not identify preoperative thrombocytopenia (<100 (G/l) or <150 (G/l)), postoperative thrombocytopenia, or the presence of antiagregant drug, as predictors of PHLF. We did not identify preoperative or postoperative thrombocytopenia as predictor of PHLF in a cohort of 597 patients.