Background An iterative reconstruction (IR) algorithm was introduced for clinical photon-counting detector (PCD) CT. Purpose To investigate the image quality and the optimal strength level of a quantum IR algorithm (QIR; Siemens Healthcare) for virtual monoenergetic images and polychromatic images (T3D) in a phantom and in patients undergoing portal venous abdominal PCD CT. Materials and Methods In this retrospective study, noise power spectrum (NPS) was measured in a water-filled phantom. Consecutive oncologic patients who underwent portal venous abdominal PCD CT between March and April 2021 were included. Virtual monoenergetic images at 60 keV and T3D were reconstructed without QIR (QIR-off; reference standard) and with QIR at four levels (QIR 1-4; index tests). Global noise index, contrast-to-noise ratio (CNR), and voxel-wise CT attenuation differences were measured. Noise and texture, artifacts, diagnostic confidence, and overall quality were assessed qualitatively. Conspicuity of hypodense liver lesions was rated by four readers. Parametric (analyses of variance, paired t tests) and nonparametric tests (Friedman, post hoc Wilcoxon signed-rank tests) were used to compare quantitative and qualitative image quality among reconstructions. Results In the phantom, NPS showed unchanged noise texture across reconstructions with maximum spatial frequency differences of 0.01 per millimeter. Fifty patients (mean age, 59 years ± 16 [standard deviation]; 31 women) were included. Global noise index was reduced from QIR-off to QIR-4 by 45% for 60 keV and by 44% for T3D (both, P < .001). CNR of the liver improved from QIR-off to QIR-4 by 74% for 60 keV and by 69% for T3D (both, P < .001). No evidence of difference was found in mean attenuation of fat and liver (P = .79-.84) and on a voxel-wise basis among reconstructions. Qualitatively, QIR-4 outperformed all reconstructions in every category for 60 keV and T3D (P value range, <.001 to .01). All four readers rated QIR-4 superior to other strengths for lesion conspicuity (P value range, <.001 to .04). Conclusion In portal venous abdominal photon-counting detector CT, an iterative reconstruction algorithm (QIR; Siemens Healthcare) at high strength levels improved image quality by reducing noise and improving contrast-to-noise ratio and lesion conspicuity without compromising image texture or CT attenuation values. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.