Background Use of a T2 mapping sequence in addition to the conventional knee MRI protocol increases sensitivity to early cartilage lesions but is time consuming. Purpose To test the in vitro validity of quantitative data from an accelerated parallel T2 mapping sequence (combined generalized autocalibrating partially parallel acquisition and model-based accelerated relaxometry by iterative nonlinear inversion [GRAPPATINI]) of the knee and to compare in vivo synthetic images generated with this sequence with those generated with conventional morphologic sequences. Materials and Methods T2 estimations with GRAPPATINI were validated in vitro in comparison with T2 estimations with routine multisection multiecho and reference standard single-section single-echo spin-echo T2 mapping sequences by using a Bland-Altman plot. Synthetic morphologic images (intermediate-weighted sequence, 34-msec echo time; T2-weighted sequence, 80-msec echo time) were compared in vivo with corresponding conventional morphologic turbo spin-echo 3-T sequences by three readers in consecutive patients recruited retrospectively from February to May 2018. Synthetic and conventional morphologic images were compared by using rates of interreader agreement, κ statistics, and rates of findings. Results T2 values with GRAPPATINI were accurate compared with those obtained with the reference single-section single-echo sequence, with slight T2 overestimation (2.7 msec). Sixty-one patients (mean age, 43 years ± 16 [standard deviation]; 32 men) were included. The rate of agreement when one reader used synthetic morphologic images and the other used conventional sequences was not inferior to the rate of agreement when all readers used conventional sequences (upper bounds of 95% confidence intervals of differences between rates of agreement ≤ 4.8%). Interreader agreement was similar for the conventional set alone, the synthetic set alone, and when readers used different sets (two-by-two differences between κ values for all items ≤ 0.15). The rates of findings were not different between synthetic and conventional image sets (all P ≥ .07) except for two items (femoral trochlear cartilage [3.0% vs 0.3%, P = .006] and joint effusion [0.3% vs 2.7%, P = .005]). Conclusion This T2 mapping sequence yields, in one acquisition, accurate T2 values and synthetic morphologic images that are comparable with those obtained with conventional turbo spin-echo sequences. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Fritz in this issue.