BackgroundMediastinal lesions are diagnosed sometimes by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Wet-heparinized suction technique has been used to improve the quality of abdominal solid tumor samples obtained by EUS-FNA. The aim of the study is to assess the effect of wet-heparinized suction on the quality of mediastinal solid tumor samples and to evaluate the safety of the method.MethodsThe medical records, EUS-FNA records, pathologic data, and follow-up data between the patients who suspected mediastinal lesions with wet-heparinized suction and conventional suction were retrospectively and comparatively analyzed. Adverse events at 48 h and 1 week after EUS-FNA were evaluated.ResultsWet-heparinized suction contributed to more tissue specimens (P< 0.05), superior tissue integrity (P< 0.05), and a longer length of white tissue core (P< 0.05). In addition, the more complete the tissue bar was, the higher the rate of successful sample (P< 0.05). Moreover, the total length of the white tissue bar at the first puncture was remarkably longer in the Experimental group (P< 0.05). No significant difference in red blood cell contamination in paraffin sections was found between the two groups (P> 0.05). There was no complication after discharge in both groups.ConclusionWet-heparinized suction can improve the quality of mediastinal lesion samples obtained by EUS-FNA and increase the success rate of sampling. In addition, it will not aggravate blood contamination in paraffin sections while ensuring a safe puncture.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-023-02845-w.