The OptoTIRF is a compact and powerful, yet inexpensive, motorized TIRF illuminator designed to fit onto most research-grade inverted microscopes. It gives the researcher intuitive and dynamic access to the entire back aperture of the objective with joystick or software control and simple storage and recall of preset positions. This makes it suitable for acquisition protocols involving TIRF and/or oblique illumination at a range of penetrations, depths, and wavelengths. Full 360° positioning and the ability to image at multiple points makes the OptoTIRF straightforward to adjust the illumination to the sample and to minimize fringes or shading gradients. The OptoTIRF also supports multi-mode fibers allowing the use of higher power and less expensive multi-mode lasers for high-speed localization microscopy. Flexibility is further enhanced by a motorized tube lens for automatic correction for different height sample dishes, or different magnification TIRF lenses, and a motorized bypass for widefield illumination using LEDs or a liquid light guide.