Objectives: To compare the vital sign stability and cost of two commonly used sedatives, midazolam (MDZ) and dexmedetomidine (DEX). Patients and Methods: This retrospective study targeted patients who underwent mandibular third molar extractions under intravenous sedation using MDZ or DEX. The predictor variable was the type of sedative used. The primary outcome variables were vital signs (heart rate and blood pressure), vital sign outliers, and cost of the sedatives. A vital sign outlier was defined as a 30% or more change in vital signs during sedation; the fewer changes, the higher the vital sign stability. The secondary outcome variables included the observer's assessment of alertness/sedation scale, level of amnesia, patient satisfaction, and bispectral index score. Covariates were sex, age, body mass index, sleeping time, dental anxiety score, and Pederson scale. Descriptive statistics were computed including propensity score matching (PSM). The P-value was set at 0.05. Results: The study enrolled 185 patients, 103 in the MDZ group and 82 in the DEX group. Based on the data after PSM, the two samples had similar baseline covariates. The sedative effect of both agents was satisfactory. Heart rate outliers were more common with MDZ than with DEX (49.3% vs 22.7%, P=0.001). Heart rate was higher with MDZ (P=0.000). The cost was higher for DEX than for MDZ (29.27±0.00 USD vs 0.37±0.04 USD, P=0.000). Conclusion: DEX showed more vital sign stability, while MDZ was more economical. These results could be used as a reference to guide clinicians during sedative selection.