A surgical instrument holder has a head assembly and a drive spindle assembly. The head has a second coupling end with a coupling device and interface for receiving and holding a surgical instrument. The instrument is held by a releasable locking mechanism having a ring slideably biased against the coupling device by a spring, and a connection device retaining the spring in a fixed position during use. The spindle assembly has a drive spindle rotatably housed in a cylindrical tube. The connection device provides a quick-release connection between the head and drive spindle assemblies, such that unlocking the connection device enables quick disassembly of the connection for cleaning and component sterilization. A method of use of the instrument holder allows the surgical instrument to be installed through an incision in a least invasive orientation separate from the holder.