To compare the outcome of traditional teaching with hybrid simulation-based teaching for undergraduate medical students. Place and Duration of the Study: Department of Pharmacology, Jinnah Medical and Dental College, Karachi, Pakistan, from June to August 2023. Quasi-experimental study. One hundred students from MBBS 3rd year were included in the study after taking the informed consent. Participants were divided into two cross-over groups and sampling was done randomly. Group A: (even roll numbers, n = 50) was the control group, taught by traditional lecture on positive inotropic medicines. Group B: (with odd roll numbers, n = 50) was the intervention group, taught the same topic by simulation-based teaching through 5 case scenarios. The teaching of this group was reinforced by role plays. Scores of post-test and retention test were compared by applying the Student's t-test. Students taught by traditional lectures i.e., Group A, their post-test mean scores were 30.7 ± 5.6, whereas Group B scored 45.7 ± 3.3, taught by hybrid stimulation (p <0.001). Retention test (MCQs based) was conducted after one month in which Group A obtained a mean score of 18.8 ± 9 with a passing percentage of approximately 30, whereas Group B obtained a score of 41.3 ± 5.6 (p <0.001). Hybrid-simulation-based teaching improved the immediate test scores as well as retention. Traditional teaching, Hybrid-simulation, MCQs, Retention test, Intervention group.