E-learning is frequently integrated into dental education, yet little is known on the effectiveness of e-learning in both instilling foundational knowledge and facilitating translation of newly acquired knowledge and skill into clinical application. The objective of this study was to investigate the impact of learning modality on acquisition of knowledge and translation to clinical skill using objective feedback from oral anesthesia manikins and subjects' self-reported confidence scores. This mixed-method study involved first year dental students (n=52) who volunteered to participate in a learning intervention, simulation exercise, and survey in 2022. Students were randomly assigned to lecture (n=26) or e-learning (n=26) cohorts and then participated in the intervention, postintervention assessment, and a simulation to evaluate correct approaches for each dental block and attempts to success. All subjects scored significantly higher on post-intervention assessment compared to pre-intervention assessment (8.2vs. 5.9; p<0.0001) with no significant differences between intervention groups when comparing preintervention and postintervention scores. Furthermore, there were no significant differences between the two cohorts when comparing abilities to correctly approach each dental block or attempts to success. Finally, all students reported a significant increase in confidence in most categories following intervention and simulation, with no significant differences between lecture and e-learning cohorts. Our findings suggest students learning via e-learning are equally capable as those learning via lecture at demonstrating newly acquired knowledge and skill in both assessments and clinical simulations. Results support incorporating supplemental e-learning and oral anesthesia manikin exercises for students learning the anatomy of dental injections.