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99m Tc-Technegas was recently approved by the U.S. Food and Drug Administration as a radiopharmaceutical for ventilation scintigraphy. However, there are currently no data comparing the quantification of relative lung ventilation with 99m Tc-Technegas with that performed using the standard approach with inhaled 133 Xe. Methods: We performed a secondary analysis of data from prospectively recruited participants in a phase 3 trial undergoing evaluation for lung transplantation who received both 133 Xe and 99m Tc-Technegas ventilation imaging. The 133 Xe and 99m Tc-Technegas images were analyzed asynchronously using semiautomatic segmentation to extract the relative lung ventilation percentages. The anterior and posterior 99m Tc-Technegas images were analyzed to derive 3 sets of relative ventilation percentages (posterior, anterior, and geometric mean data) and compared with the values from posterior 133 Xe images. We evaluated for correlation and agreement between the relative lung ventilation percentages obtained using these 2 radiopharmaceuticals. Results: In a cohort of 74 participants, we found a strong positive correlation in the relative lung ventilation quantified using 133 Xe with that using 99m Tc-Technegas. A high level of agreement was demonstrated on the Bland-Altman plot comparing the 2 imaging modalities. Seventy-two of 74 participants (97.3%) had their relative ventilation percentage measurements within ±15% for 133 Xe and 99m Tc-Technegas. The differences in relative ventilation measurements were within the 95% CI limits of the mean for 70 of 74 participants (94.6%) and within a narrower ±10% threshold for 68 of 74 participants (91.9%), again reflecting the comparability of the 2 techniques. The strongest correlation coefficient ( r = 0.79) was observed between the relative ventilation percentages obtained from 133 Xe and posterior 99m Tc-Technegas images. The geometric mean method had a slightly lower but still comparable correlation ( r = 0.77), and as expected, the correlation with the anterior 99m Tc-Technegas images was worst ( r = 0.70). Conclusion: We showed a strong positive correlation and high agreement between the relative lung ventilation percentages obtained using 133 Xe and 99m Tc-Technegas. These data provide important clinical evidence supporting the use of 99m Tc-Technegas for quantification of relative lung ventilation., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)