troubleshooting Question

One large VMDK file or smaller ones

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Now with esxi 5.5, we can have 64 TB vmdk files, but is there a performance benefit of having multiple vmdk's in multiple datastores, or just having one large vmdk?  I could see the benefit for a large number of vmdk's and VM's, but if it's just for backup purposes using MS DPM, is there any reason I should consider one over the other?  Thanks.
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