Background/Aims: We aimed to study the effects of sedation on endoscopic ultrasound–guided tissue acquisition. Methods: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound–guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS). Results: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234–1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in the ACP group and 66/106 (62.3%) in the CS group, respectively (p=0.0274). In multivariate analysis, the difference in diagnostic yield between the two groups was not significant (aOR, 0.643; 95% CI, 0.356–1.159; p=0.142). A total of 33 adverse events (AEs) were observed. The incidence of AEs was significantly lower in the CS group (5/33 CS vs. 28/33 ACP; OR, 0.281; 95% CI, 0.095–0.833; p=0.022). Conclusions CS provided equivalent technical success and diagnostic yield for malignancy in endoscopic ultrasound–guided tissue acquisition. Increased AEs were associated with anesthesia for the endoscopic ultrasound–guided tissue acquisition.