Purpose: To prospectively evaluate topographical and sex variations in the T-2 relaxation values of tibiotalar cartilage (TTC) of healthy young adults. Materials and Methods: Sagittal 8-echo multiecho spin-echo T-2 maps of TTC were acquired using a 3.0T MR in 25 male and 25 female healthy young adult participants. Quantitative measurements of T-2 values in tibial cartilage (TBC) and talar cartilage (TLC) were obtained from three zones (anterior zone, AZ; middle zone, MZ; and posterior zone, PZ) and from four compartments (medial compartment, MC; midmedial compartment, MMC; midlateral compartment, MLC; and lateral compartment, LC) of TBC and TLC in the sagittal plane. Results: The T-2 values of AZ (for TBC, 29.31 msec; for TLC, 35.81 msec) and MZ (for TBC, 28.56 msec; for TLC, 36.12 msec) in males were significantly higher than those in females (for AZ of TBC, 26.99 msec; for AZ of TLC, 33.56 msec; for MZ of TBC, 25.88 msec; for MZ of TLC, 31.85 msec) (for TBC, AZ, P = 0.009, MZ, P = 0.002; for TLC, AZ, P 5 0.047, MZ, P = 0.001). Except for MMC and MLC of TBC (MMC, P = 0.02, MLC, P = 0.03), TTC T-2 values did not differ significantly between these compartment in either group (for TBC, MC, P = 0.27, LC, P = 0.37; for TLC, MC, P = 0.26, MMC, P = 0.08, MLC, P = 0.30, LC, P = 0.10). Conclusion: We found significant sex and topographic variations among TTC T-2 values of healthy young adults. Acknowledgment of the significant topographical and sex variations in cartilage T-2 values may minimize misinterpretation of ankle joint TTC T-2 mapping data.