Objective: To quantify the precision and accuracy of measurements of joint space width (JSW) and joint space narrowing (JSN) from the medial tibiofemoral compartment of knee radiographs using a simple and easily adaptable protocol. Methods: Radiographs of a caliper (a surrogate for JSW) were obtained to determine the precision limits of the system under ideal conditions. Bilateral knee radiographs from 10 healthy volunteers were obtained at three different times using the metatarsophalangeal (MTP) semi-flexed view posterior–anterior position without fluoroscopy. A backlit digitizing tablet and three manual methods were used to measure JSW and analyses of precision were performed. The accuracy of measuring change in JSW (a measure of JSN) was estimated from radiographs of cadaver knees that were placed in a servo-hydraulic device that moved the femur relative to the tibia through known intervals. Results: Radiographic measurements of the caliper inter-blade distance were comparable to the resolution limits of the backlit digitizing tablet (0.025 mm). Repeated radiography of healthy subject knees produced JSW standard deviation (SD) measurements of 0.08 mm by the median SD method, and 0.11 mm by repeated measures analysis. The accuracy of JSN measurements in the cadaver knees as a mean difference from the known reference value was 0.09 mm. Conclusion: The results indicate a high level of precision in measurements of JSW from MTP semi-flexed view knee radiographs of normal volunteers. Reproducibility was attained through careful subject positioning without fluoroscopy and the use of a backlit digitizing tablet. From the cadaver study we can predict that greater than 0.13 mm of measured JSN represents actual or true change in JSN. This radiographic technique can be used as a primary measure for early knee osteoarthritis (OA) when cartilage thickness is decreasing and limited bony remodeling has occurred.