Background CT manifestations of SARS-CoV-2 may differ among variants. Purpose To compare the chest CT findings of SARS-CoV-2 between the Delta and Omicron variants. Materials and Methods This retrospective study collected consecutive baseline chest CT images of hospitalized patients with SARS-CoV-2 from a secondary referral hospital when the Delta and Omicron variants were predominant. Two radiologists categorized CT images according to the RSNA classification system for COVID-19 and visually graded pneumonia extent. Pneumonia, pleural effusion, and intrapulmonary vessels were segmented and quantified on CT images using a priori–developed neural networks, followed by reader confirmation. Multivariable logistic and linear regression analyses were performed to examine the associations between the variants and CT category, distribution, severity, and peripheral vascularity. Results In total, 88 patients with the Delta variant (mean age, 67 years ± 15 [SD]; 46 men) and 88 patients with the Omicron variant (mean age, 62 years ± 19; 51 men) were included. Omicron was associated with less frequent, typical peripheral bilateral ground-glass opacity (32% [28 of 88] vs 57% [50 of 88], P = .001), more frequent peribronchovascular predilection (38% [25 of 66] vs 7% [five of 71], P < .001), lower visual pneumonia extent (5.4 ± 6.0 vs 7.7 ± 6.6, P = .02), similar pneumonia volume (5% ± 1 vs 7% ± 11, P = .14), and a higher proportion of vessels with a cross-sectional area smaller than 5 mm2 relative to the total pulmonary blood volume (BV5%; 48% ± 11 vs 44% ± 8; P = .004). In adjusted analyses, Omicron was associated with a nontypical appearance (odds ratio, 0.34; P = .006), peribronchovascular predilection (odds ratio, 9.2; P < .001), and higher BV5% (β = 3.8; P = .01) but similar visual pneumonia extent (P = .17) and pneumonia volume (P = .67) relative to the Delta variant. Conclusion At chest CT, the Omicron SARS-COV-2 variant showed nontypical peribronchovascular pneumonia and less pulmonary vascular involvement than did th...