Strengthening building structures to mitigate their likelihood of disproportionate collapse, due to initial damage produced by abnormal loads, has a significant impact on construction costs. The decision to strengthen or not needs to be taken under significant epistemic uncertainty related to potential blast hazard scenarios and threat probabilities. In this manuscript we present a novel risk-based cost-benefit analysis to address optimal and codified design options for RC buildings subject to blast hazards. Building frames of different aspect ratios (number of bays × number of stories) are addressed. Three terrorist blast hazard scenarios are considered: two VBIEDs and one smaller suitcase bomb. The large uncertainty in threat likelihood is addressed by treating annual threat probability as the independent parameter in the analyses. This makes the blast hazard analysis, and the progressive collapse analysis, independent of the factors that can make a particular building a target, like location, environment, ownership, and use. The analysis reveals the break-even hazard (threat) probabilities, which make the cost of structural strengthening equal to the reduction in expected cost of progressive collapse. For a particular building location, use, and blast threat, if the hazard probability is larger than the break-even probability, strengthening is cost-effective. The break-even point between the choices of strengthening with removal of a single or of two columns is also presented and discussed. Practical recommendations for codified Alternate Path Method include a distinction between strengthening factors for beams and columns, much in the same way as already done in conventional design.