Many different engineering tasks are performed in support of operation of nuclear power plants with the aim of carrying out an effective and safe exploitation. Among such activities maintenance, core follow-up, refuelling and analyzing operating experience are the most commonly cited. Thermal-hydraulic analysis is an important issue that could help many different aspects of the engineering activity taking care of plant operation. Integral Plant Models prepared using system codes are a valuable tool to carry out analytical activities devoted to contribute to engineering support to plant operation. Most of the issues and tasks presented in the chapter are part of the job description of the so called thermalhydraulic analyst supporting plant operation (Reventos, 2008). Usually, this analyst is an engineer belonging to the technical team that takes care of engineering plant support. In many plants such engineer takes care of plant models and he personally performs at least the first approach analysis of any of the issues involved. Depending on the amount of work needed to carry out each specific analysis the whole work or only a part of it is done by him. In the first case the benefits are clear since he knows the plant and he uses the information produced or treated by the team he belongs to. In the second case, when the amount of work is too large, the thermalhydraulic analyst will take care of the technical subcontracting of the analysis. The benefits in this latter case are also clear since he is coordinating a task well known to his own calculating experience. This chapter has three different sections. The first one gives some detail on thermalhydraulic analysis tasks related to operation. The second clarifies some features that are specific of Integral Plant Model. Especially, it establishes how the nodalization is qualified. Finally, the third briefly presents some relevant results of one example of analysis performed in such context along with the concise description of other two cases.