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http://www.ioncube.com/faq.php#zo2

Q. Can I install Zend Optimizer with the Loader?
A. Yes. We permit trusted software to be installed, and so we support the installing of Zend Optimizer along with our Loader in the php.ini file. Note that our Loader must be installed before Zend Optimizer in the php.ini file. If you do see messages claiming any incompatibility then this is incorrect and will be a configuration problem. Please let us know and we'll let you know what's wrong.