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On Mac OS X Google Chrome writes it's settings on the file:

~/Library/Application Support/Google/Chrome/Default/Preferences

When updating a setting through the Chrome UI the correct value is written to the file. When updating the value on the file (with Chrome closed), on load Chrome rewrites previous values to this file.

Is there a way to make Chrome not ignore my changes on it? Must I use Google's UI to change preferences?

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I'm having the same problem, and the setting I need to update doesn't have a UI entry. Super frustrating. – Tom Thorogood May 19 '12 at 11:57

The cause of this is Chrome syncing the Preferences file with an online Google Account. To prevent syncing the Preferences file on startup, use the following command:

google-chrome --disable-sync-preferences

If this option is removed in the future, then an alternative would be to disable syncing entirely either through the UI or through the "--disable-sync" switch. I discovered these switches from the reference page of Chrome Engineer Peter Beverloo:

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