OBJECTIVE. To determine whether a high-fidelity simulation technique compared with lecture would produce greater improvement in advanced cardiac life support (ACLS) knowledge, confidence, and overall satisfaction with the training method. DESIGN. This sequential, parallel-group, crossover trial randomized students into 2 groups distinguished by the sequence of teaching technique delivered for ACLS instruction (ie, classroom lecture vs high-fidelity simulation exercise). ASSESSMENT. Test scores on a written examination administered at baseline and after each teaching technique improved significantly from baseline in all groups but were highest when lecture was followed by simulation. Simulation was associated with a greater degree of overall student satisfaction compared with lecture. Participation in a simulation exercise did not improve pharmacy students' knowledge of ACLS more than attending a lecture, but it was associated with improved student confidence in skills and satisfaction with learning and application. CONCLUSIONS. College curricula should incorporate simulation to complement but not replace lecture for ACLS education.