Introduction: The aims of this study were to observe the therapeutic effect of platelet (PLT) transfusion and to analyze influencing factors for the sake of providing useful clues for improving the efficacy of PLT transfusion. Methods: Included in this study were patients who received PLT transfusion in the affiliated hospital of Nantong University. Patients’ sex, age, height, weight, PLT transfusion status, and 20–24-h PLT count before and after PLT transfusion were collected to calculate the PLT corrected count increment values before and after PLT transfusion. Solid-phase red cell adherence assay was used to determine PLT antibody. Statistical analysis was performed using SPSS25.0 Software. Results: A total of 364 patients received 1,060 PLT transfusions, including 728 successful transfusions and 332 unsuccessful transfusions. When the patients were grouped according to different etiologies, significant differences in PLT transfusion effectiveness were observed between these groups (χ2 = 15.070, p < 0.05). Grouping of the 364 patients according to sex, blood type, and PLT transfusion frequency showed no significant difference in PLT transfusion refractoriness (PTR) between different age-groups and sexes (p > 0.05). With the number of PLT transfusions increasing, PTR increased gradually. PLT antibodies were detected of 364 patients, 67 of them were positive. Among them, 63 cases (94.02%) were positive for HLA class I antibody. Conclusion: To reduce PTR, multiple factors should be considered comprehensively when PLT transfusion therapy is to be implemented in clinical practice. PLT antibody is the main immune factor causing PTR.