Osteoarthritis (OA) is a prevalent disease and the leading cause of pain, disability, and quality of life deterioration. Our study sought to evaluate the image quality and dose of cone-beam computed tomography arthrography (CBCT-A) and compare them to digital radiography (DR) for OA diagnoses. Overall, 32 cases of CBCT-A and DR with OA met the inclusion criteria and were prospectively analyzed. The Kellgren and Lawrence classification (KLC) stage, sclerosis, osteophytes, erosions, and mean joint width (MJW) were compared between CBCT-A and DR. Image quality was excellent in all CBCT-A cases, with excellent inter-observer agreement. OA under-classification was noticed with DR for MJW (p = 0.02), osteophyte detection (<0.0001), and KLC (p < 0.0001). The Hounsfield Unit (HU) values obtained for the cone-beam computed tomography CBCT did not correspond to the values for multi-detector computed tomography (MDCT), with a greater mean deviation obtained with the MDCT HU for Modeled Based Iterative Reconstruction 1st (MBIR1) than for the 2nd generation (MBIR2). CBCT-A has been found to be more reliable for OA diagnosis than DR as revealed by our results using a three-point rating scale for the qualitative image analysis, with higher quality and an acceptable dose. Moreover, the use of this imaging technique permits the preoperative assessment of extremities in an OA diagnosis, with the upright position and bone microarchitecture analysis being two other advantages of CBCT-A.