Background and Objectives: The negative pressure selectable for the wet-suction technique remains uncertain. The aim was to investigate the quality of sampling and diagnostic accuracy with solid lesions by 5 mL and 10 mL negative pressure with wet-suction techniques. Methods: This is a single-center, crossover, randomized controlled trial conducted with a random sampling technique. In all, 160 patients consecutively undergoing EUS-FNA for solid lesions were randomized in a ratio of 1:1 into 2 groups, the 5 mL and 10 mL negative pressure wet-suction group. The main outcome was to compare the sample quality between the 2 groups. The secondary outcome was to compare the histologic and cytologic diagnostic accuracy of solid lesions. Results: Pancreatic (n=129) and nonpancreatic (n=27) lesions from 156 lesions were examined. The sample quality concluding cellularity, adequacy, integrity, and blood contamination were comparable between the 2 groups. However, in subgroup analysis, we found 19G FNA provided more integrity of specimen in 5 mL than in 10 mL group (100% vs. 82.9%, P=0.025). In contrast, this benefit was not noteworthy in the 22G FNA subgroup. And there was no statistically significant in histologic (87.82% vs. 87.18%, P=1.000) and cytologic (78.85% vs. 80.77%, P=0.778) accuracy between 5 mL and 10 mL groups. Conclusion: When using the wet-suction technique, 5 mL and 10 mL negative pressure offer equivalent sample quality and diagnostic accuracy. However, the 19G FNA can obtain better sample quality with 5 mL negative pressure than 10 mL negative pressure.