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GPS-denied closed-loop autonomous control of unstable Unmanned Aerial Vehicles (UAVs) such as rotorcraft using information from a monocular camera has been an open problem. Most proposed Vision aided Inertial Navigation Systems (V-INSs) have been too computationally intensive or do not have sufficient integrity for closed-loop flight. We provide an affirmative answer to the question of whether V-INSs can be used to sustain prolonged real-world GPS-denied flight by presenting a V-INS that is validated through autonomous flight-tests over prolonged closed-loop dynamic operation in both indoor and outdoor GPS-denied environments with two rotorcraft unmanned aircraft systems (UASs). The architecture efficiently combines visual feature information from a monocular camera with measurements from inertial sensors. Inertial measurements are used to predict frame-to-frame transition of online selected feature locations, and the difference between predicted and observed feature locations is used to bind in real-time the inertial measurement unit drift, estimate its bias, and account for initial misalignment errors. A novel algorithm to manage a library of features online is presented that can add or remove features based on a measure of relative confidence in each feature location. The resulting V-INS is sufficiently efficient and reliable to enable real-time implementation on resource-constrained aerial vehicles. The presented algorithms are validated on multiple platforms in real-world conditions: through a 16-min flight test, including an autonomous landing, of a 66 kg rotorcraft UAV operating in an unconctrolled outdoor environment without using GPS and through a Micro-UAV operating in a cluttered, unmapped, and gusty indoor environment. © 2013 Wiley Periodicals, Inc.