A risk analysis for a pilot scale-freeze-dryer is shown in this paper, aiming to build the basis for the risk-based decision making in plant and process design of a (pilot scale) freeze-dryer, to be then exploited in the design of a full Scale safer plant. The risk analysis Was performed Using the recursive operability analysis to point out the process top events and to identify their primary causes. The top events here considered are the undesired freezing velocity in the freezing stage and the undesired heating profile and/or pressure value in the whole process, as they can be responsible for product overheating and, thus, jeopardize product quality. After the extraction of the fault trees, the minimal cut-sets were identified. The unavailability at mission time Was then calculated) and the contribution of the primary causes to the top events occurrence was evaluated. The more critical plant components were identified, and a suitable 2(k) Design of Experiments was set up to evaluate how the uncertainty on the values of the failure rates of the various components affect the unavailability at mission time.