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I think the best way (if using ePO 4.0) is using the AD mirroring task i.e. if you delete any computer from your AD it will be automatically deleted from your ePO directory at next AD replication task
I'm using version 22.214.171.1248 if that helps anyone..
for me, i'm taking the assumption that a machine that doesnt report in for more than 30days had been removed from our network. so i use the 'last update' field for this purpose.
hope this helps somewhat.