The LOng Range Reconnaissance Imager (LORRI) is a panchromatic (360--910 nm), narrow-angle (field of view = 0.29 deg), high spatial resolution (pixel scale = 1.02 arcsec) visible light imager used on NASAs New Horizons (NH) mission for both science observations and optical navigation. Calibration observations began several months after the NH launch on 2006 January 19 and have been repeated annually throughout the course of the mission, which is ongoing. This paper describes the in-flight LORRI calibration measurements, and the results derived from our analysis of the calibration data. LORRI has been remarkably stable over time with no detectable changes (at the 1% level) in sensitivity or optical performance since launch. By employing 4 by 4 re-binning of the CCD pixels during read out, a special spacecraft tracking mode, exposure times of 30 sec, and co-addition of approximately 100 images, LORRI can detect unresolved targets down to V = 22 (SNR=5). LORRI images have an instantaneous dynamic range of 3500, which combined with exposure time control ranging from 0ms to 64,967 ms in 1ms steps supports high resolution, high sensitivity imaging of planetary targets spanning heliocentric distances from Jupiter to deep in the Kuiper belt, enabling a wide variety of scientific investigations. We describe here how to transform LORRI images from raw (engineering) units into scientific (calibrated) units for both resolved and unresolved targets. We also describe various instrumental artifacts that could affect the interpretation of LORRI images under some observing circumstances.