Military and civilian first-responders must be able to recognize and effectively manage mass disaster casualties. Clinical management of injuries resulting from nerve agents provides different challenges for first responders than those of conventional weapons. We evaluated the impact of a mixed-methods training program on competency acquisition in cholinergic crisis clinical management. Methods: We developed a multimedia and simulation-based training program based on the more comprehensive USAMRICD courses. The training program was designed to provide first-responders with the necessary abilities to recognize and manage a mass casualty cholinergic crisis event. Training included a learner controlled multimedia iPad app and hands-on instruction using SimMan3Gâ„¢ mannequin simulators. We evaluated the impact of the training through a purposively selected sample of 204 civilian and military first responders who had not previously completed either of the referenced USAMRICD courses. We assessed knowledge, performance, affect, and self-efficacy measures pre- and post-training using previously validated assessment instruments. We calculated results using analysis of variance with repeated measures, and with statistical significance set at p < .05. Results: Analyses demonstrated a significant improvement (p = .000) across all domains (knowledge, performance, self-efficacy, and affect). Knowledge scores increased from 60% to 81% correct. Performance scores increased from 16% to 68% correct. Self-efficacy scores increased from 51% to 87% confidence in ability to effectively manage a cholinergic crisis event. Affect scores increased from 75% to 81% personal comfort during procedures. Conclusions: These findings could aid in the selection of instructional methodologies available to a broad community of first-responder personnel in military and civilian service. Although less comprehensive than the USAMRICD courses, training outcomes associated with this easily distributed instruction set demonstrated its value in increasing the competency of first responders in recognizing and managing a mass casualty cholinergic event. Retention outcomes are in process.