Background: T2 mapping is a recognized magnetic resonance imaging (MRI) technique that reflects collagen fiber organization and tissue hydration, making it sensitive to early biochemical changes in cartilage. Evaluating an accelerated GRAPPATINI sequence and comparing its performance to conventional methods is crucial for reliable cartilage evaluation. This study aims to evaluate and compare T2 relaxation times in healthy knee cartilage using a conventional multi-echo spin-echo (MESE) sequence and the accelerated GRAPPATINI sequence, and to assess their reliability in a test-retest design. Methods: All patients underwent a baseline MRI, followed by imaging at 3, 6, and 12 months as part of a prospective national study protocol. Sagittal T2 mapping with both MESE and GRAPPATINI sequences was acquired. Regions of interest were drawn in morphologically normal cartilage of the medial femoral condyle, lateral femoral condyle, and patella, segmented by depth (superficial, intermediate, deep). T2 values were compared using linear mixed-effects model. Agreement between methods was evaluated with Bland-Altman analysis, and repeatability was assessed with correlation, regression, and intraclass correlation coefficients (ICC). Results: Nine patients (mean age 38 years, 6 males and 3 females) underwent acquisition of both T2 mapping sequences in 22 MRI exams. Mean T2 values ranged from 30.1 to 45.2 ms with MESE, and from 27.8 to 47.7 ms with GRAPPATINI. T2 values varied significantly by cartilage depth, with longer relaxation times in superficial and intermediate layers compared to deep cartilage, independently of the sequence used. Overall, no significant differences in T2 values were observed between the MESE and GRAPPATINI sequences, except in the superficial layer of the lateral femoral condyle, where a significant difference was noted. The Bland-Altman analysis demonstrated no systematic bias between methods [mean difference: −0.26 ms; with limits of agreement of 15.7 ms (mean + 2SD) and −16.2 ms (mean − 2SD)]. Concerning the repeatability the study, a stronger correlation and higher reliability were observed with the GRAPPATINI method (R=0.73, ICC =0.75) compared to the MESE method (R=0.53, ICC =0.61). The slope of the regression line for GRAPPATINI was 0.91, indicating a high level of reproducibility between visits, whereas the MESE method yielded a lower slope of 0.56. When considering all anatomical areas and cartilage depths combined, ICC values were consistently higher for GRAPPATINI than for MESE. Conclusions: Both MESE and GRAPPATINI provide consistent T2 mapping of knee cartilage, but GRAPPATINI achieves greater reliability with shorter acquisition time. Depth-dependent differences in T2 highlight the importance of layer-specific evaluation in quantitative cartilage assessment.