Inherited macrothrombocytopenia (IMT) is characterized by increased platelet volume. Using platelet parameters, including platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR), and platelet distribution width, to differentiate IMT from acquired thrombocytopenia (AT) in the Chinese population is unclear. This study aimed to evaluate these parameters and determine optimal thresholds for early IMT identification. This single-center, retrospective case-control study included IMT patients from 1 January 2022 to 31 January 2024. Age- and sex-matched AT patients and healthy individuals were selected (1:3 ratio). Platelet parameters were compared using a one-way analysis of variance and the Kruskal-Wallis test. The ability of platelet parameters to identify IMT was assessed using the receiver operating characteristic curve, with the optimal threshold determined using the Youden index. This study included 13 IMT patients, 39 AT patients, and 39 controls. The MPV and P-LCR were significantly higher in IMT than in AT patients (P < 0.05) and strongly differentiated between groups. The area under the curve (95% confidence interval) for MPV and P-LCR were 0.865 (0.724-1.000) and 0.860 (0.719-1.000), respectively. The optimal MPV and P-LCR thresholds for IMT were 14.55 fL and 58%, respectively. The MPV was most important for distinguishing IMT from patients with thrombocytopenia.