This retrospective study evaluated the reproducibility and workflow efficiency of a novel software tool for quantitative coronary plaque characterization on coronary CT angiography (CCTA), comparing conventional energy-integrating detector CT (EID-CT) with photon-counting detector CT (PCD-CT). A total of 170 patients were included, 86 of them scanned with EID-CT and 84 with dual-source PCD-CT. Quantitative plaque analysis was performed on 550 coronary lesions by three experienced readers using the prototype software syngo.CT Coronary Cockpit and the reference platform MEDIS QAngioCT. The prototype software significantly reduced analysis time compared with the reference tool, with mean measurement times of 3.9 ± 2.5 versus 22.9 ± 8.8 minutes (p < 0.001), while maintaining excellent intra- and interobserver reproducibility across both CT technologies (intraclass correlation coefficient: 0.995–0.998). Median total plaque volume values significantly differed between software platforms, measuring 67.0 mm³ with the prototype tool and 50.8 mm³ with the reference software (p < 0.001). PCD-CT demonstrated improved agreement between software platforms, with lower mean bias compared with EID-CT (15.0 vs. 45.3 mm³), while also reducing discrepancies between automated and manual plaque measurements. Overall, the findings suggest that the prototype software supported by advanced CCTA may provide rapid and highly reproducible coronary plaque quantification, with PCD-CT further reducing inter-platform variability and the need for manual corrections.