Abstract Background and Aims: Inhalation anesthetics is basic knowledge that must be mastered by an anesthesiologist. Lack of competencies can result in higher morbidity and mortality in anesthesiology practice. Various learning methods were developed to improve understanding and retention. With the advancement of technology, the utilization of screen-based simulation (SBS) using applications is common, such as the Gas Man® application, to help students understand physiology, pathophysiology, and kinetic inhalation anesthetic agents. The primary objective of this study was to compare the knowledge improvement of anesthesia residents between the simulation-based and discussion-based learning methods on the uptake and distribution of anesthetic inhalation. The secondary objective was to compare the satisfaction levels of participants in both learning methods. Material and Methods: This study is a randomized controlled trial involving anesthesiology and intensive care residents from the Faculty of Medicine, Universitas Indonesia (FKUI) 2022–2023. The participants were randomized into two groups (simulation and discussion groups). A senior attending anesthesiologist led the discussion. The participants answered a pretest, followed by a 1-hour lecture about inhalation gas. Lastly, participants answered a posttest and filled in the satisfaction survey. Statistical analyses used the Mann–Whitney test to compare the two groups. The Wilcoxon test was used to compare the knowledge improvement between the two groups. Results: Thirty-eight residents underwent simulation-based (n = 19) and discussion-based (n = 19) learning methods. The simulation group demonstrated a median (interquartile range) posttest score of 80 (76.67–83.33) compared with the discussion group with a score of 50 (40–66.67) (P value <0.05). More than half of the participants in both groups answered “satisfied.” Conclusion: The simulation-based learning method using the Gas Man® application performed better than the discussion-based learning method on increasing knowledge of the uptake and distribution of inhalation anesthetics in anesthesia residents. Key Message: Simulation-based learning method may improve understanding and retention. This study supported the conclusion that the simulation-based learning method with Gas Man is better than the discussion-based learning method for improving knowledge of the uptake and distribution of inhalation anesthetics.