Developing innovation in medical education is a vital part of improving the learning outcomes. One such learning innovation in medical education is to learn using game as a tool. The Husenynov antihypertensive drug game (HAG) was developed as an innovation to assist the learning process for studying pharmacology. The study was conducted to compare the effectiveness of HAG and traditional educational method (lecture) on knowledge and perception of medical students. A quantitative cross-sectional study was conducted with 221 second year students from the Universitas Padjadjaran Faculty of Medicine. There were two subject groups: the game group and the lecture group. Duration (two hours) and learning content were similar for both activities. A pre-post test was performed to compare the percentage of students with increased knowledge between groups, while a questionnaire of perception was distributed at the end of the study. The number of students who experienced increased knowledge (post-test score better than pre-test score) was higher in the game group than the lecture group (68% vs 54%, respectively). Students who played the game had a knowledge score 1.8 times higher compared to those who had the lecture (crosstab, OR 1.8 (95% CI 1.04-3.09)). Furthermore, a significantly higher proportion of students had positive perceptions regarding the learning method in the game group (83% vs 45%, p < 0.01). The Husenynov antihypertensive drug game (HAG) promotes better-increased knowledge and positive perceptions than the traditional educational method (lecture).