Background: MRI acceleration using deep learning (DL) convolutional neural networks (CNNs) is a novel technique with great promise. Increasing the number of convolutional layers may allow for more accurate image reconstruction. Studies on evaluating the diagnostic interchangeability of DL reconstructed knee magnetic resonance (MR) images are scarce. The purpose of this study was to develop a deep CNN (DCNN) with an optimal number of layers for accelerating knee magnetic resonance imaging (MRI) acquisition by 6-fold and to test the diagnostic interchangeability and image quality of nonaccelerated images versus images reconstructed with a 15-layer DCNN or 3-layer CNN. Methods: For the feasibility portion of this study, 10 patients were randomly selected from the Osteoarthritis Initiative (OAI) cohort. For the interchangeability portion of the study, 40 patients were randomly selected from the OAI cohort. Three readers assessed meniscal and anterior cruciate ligament (ACL) tears and cartilage defects using DCNN, CNN, and nonaccelerated images. Image quality was subjectively graded as nondiagnostic, poor, acceptable, or excellent. Interchangeability was tested by comparing the frequency of agreement when readers used both accelerated and nonaccelerated images to frequency of agreement when readers only used nonaccelerated images. A noninferiority margin of 0.10 was used to ensure type I error <= 5% and power >= 80%. A logistic regression model using generalized estimating equations was used to compare proportions; 95% confidence intervals (CIs) were constructed. Results: DCNN and CNN images were interchangeable with nonaccelerated images for all structures, with excess disagreement values ranging from -2.5% [95% CI: (-6.1, 1.1)] to 3.0% [95% CI: (-0.1, 6.1)]. The quality of DCNN images was graded higher than that of CNN images but less than that of nonaccelerated images [excellent/acceptable quality: DCNN, 95% of cases (114/120); CNN, 60% (72/120); nonaccelerated, 97.5% (117/120)]. Conclusions: Six-fold accelerated knee images reconstructed with a DL technique are diagnostically interchangeable with nonaccelerated images and have acceptable image quality when using a 15-layer CNN.