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Background CT deep learning image reconstruction (DLIR) improves image quality by reducing noise compared with adaptive statistical iterative reconstruction-V (ASIR-V). However, objective assessment of low-contrast lesion detectability is lacking. Purpose To investigate low-contrast detectability of hypoattenuating liver lesions on CT scans reconstructed with DLIR compared with CT scans reconstructed with ASIR-V in a patient and a phantom study. Materials and Methods This single-center retrospective study included patients undergoing portal venous phase abdominal CT between February and May 2021 and a low-contrast-resolution phantom scanned with the same protocol. Four reconstructions (ASIR-V at 40% strength [ASIR-V 40] and DLIR at three strengths) were generated. Five radiologists qualitatively assessed the images using the five-point Likert scale for image quality, lesion diagnostic confidence, conspicuity, and small lesion (≤1 cm) visibility. Up to two key lesions per patient, confirmed at histopathologic testing or at prior or follow-up imaging studies, were included. Lesion-to-background contrast-to-noise ratio was calculated. Interreader variability was analyzed. Intergroup qualitative and quantitative metrics were compared between DLIR and ASIR-V 40 using proportional odds logistic regression models. Results Eighty-six liver lesions (mean size, 15 mm ± 9.5 [SD]) in 50 patients (median age, 62 years [IQR, 57-73 years]; 27 [54%] female patients) were included. Differences were not detected for various qualitative low-contrast detectability metrics between ASIR-V 40 and DLIR ( P > .05). Quantitatively, medium-strength DLIR and high-strength DLIR yielded higher lesion-to-background contrast-to-noise ratios than ASIR-V 40 (medium-strength DLIR vs ASIR-V 40: odds ratio [OR], 1.96 [95% CI: 1.65, 2.33]; high-strength DLIR vs ASIR-V 40: OR, 5.36 [95% CI: 3.68, 7.82]; P < .001). Low-contrast lesion attenuation was reduced by 2.8-3.6 HU with DLIR. Interreader agreement was moderate to very good for the qualitative metrics. Subgroup analysis based on lesion size of larger than 1 cm and 1 cm or smaller yielded similar results ( P > .05). Qualitatively, phantom study results were similar to those in patients ( P > .05). Conclusion The detectability of low-contrast liver lesions was similar on CT scans reconstructed with low-, medium-, and high-strength DLIR and ASIR-V 40 in both patient and phantom studies. Lesion-to-background contrast-to-noise ratios were higher for DLIR medium- and high-strength reconstructions compared with ASIR-V 40. © RSNA, 2024 Supplemental material is available for this article.