The protection of underground civil infrastructure continues to be a high priority for transportation and transit security agencies. In particular, rail transit tunnels running under bodies of water are susceptible to disruptions due to flooding caused by extraordinary climatic events such as hurricanes or other events resulting from human activities. Several events have taken place in the past decades that have demonstrated the need to mitigate vulnerabilities or, at least, minimize the consequences of catastrophic events. Although it is impossible to prevent all situations that can lead to flooding, damage can be substantially decreased by reducing the area affected by the event. To minimize the effects of an event, a possible approach is to compartmentalize the tunnel system by creating temporary barriers that can contain the propagation of flooding until a more permanent solution can be implemented. One way to create a temporary barrier is by the deployment of a large-scale inflatable structure, also known as an inflatable plug. In such an application, the inflatable structure is prepared for placement, either permanently or temporally, and maintained ready for deployment, inflation, and pressurization when needed. The internal plug pressure imparts a normal force against the tunnel wall surface with the friction between the plug and tunnel surfaces opposing axial movement of the plug. The sealing effectiveness depends on the ability of the inflatable structure to self-deploy and fit, without human intervention, to the intricacies of the perimeter of the conduit being sealed. Primary design constraints include having the plug stowed away from the dynamic envelope of the trains and being able to withhold the pressure of the flooding water. This work presents a compilation of the main aspects of the activities completed for the development of large-scale inflatable structures as part of the Resilient Tunnel Plug (RTP) Project. The main test results and lessons learned are presented to demonstrate the viability of implementing large-scale inflatable plugs for the containment of flooding in rail tunnels systems. Over 400 coupon and specimen tests, 200 reduced scale tests, and 100 full-scale tests were conducted to demonstrate the efficacy of the design of different prototypes over a 10-year research and development project. The culmination of the work was 12 large-scale flooding demonstrations where the inflatable tunnel plug was shown able to be deployed remotely and withstand a simulated flooding event.