There are two sides to the story, first it is obvious that working with a huge model and fluent will require a little bit more in terms of maintenance, however the bigger the model gets the harder it gets to work with the designer, as soon as you hit 500 entities you will face certain trouble with reponsiveness of the diagram.
What you should also take into consideration is the fact that the FluentAPI provides more (and more advanced) features than the designer. You will not get to map dictionaries, structs or use polymorphic references through the designer.
Another thing to think about is the designer wizard, that you will not be able to use with fluent, for example Upgrade From Database applies all changes to the database to your model and creates new classes for you, using the fluent you will need to either work model first, or parallely work on the schema and classes (and fluent mapping).
In a few words working with the designer is easier and faster, and if you are spiking or have no time to spare, I would suggest that you use that. However if you want full control of your model, more features and a nice code only approach, then you should use the Fluent Mapping.
(Of course, if you already have a huge database that needs mapping, there isn't much sence in going Fluent, as the initial effort of mapping everything will be quite small when using the designer).
I hope this is helpful.
the Telerik team
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