This paper develops and applies novel approaches for risk management and economic viability analysis applicable in early stages (i.e., low TRL’s) of highly uncertain, multi-staged, path-dependant technology-oriented R&D projects. It proposes (and applies in an actual R&D project) a multi-pronged, multi-staged, networked approach based on the systematic application of conditional probabilities. This approach involves identifying future “defining events” or milestones, characterized by having an identifiable set of relevant, alternative “output states”. Risk drivers and preventive actions are then linked to this multi-staged structure. A spreadsheet-based tool for tracking conditional probabilities and path dependency is described. It also discusses major stumbling blocks in its application, such as the potential combinatorial explosion, and analyses how to tackle or prevent them.