Importance: Psoriasis is a chronic inflammatory skin disease associated with increased coronary plaque burden and cardiovascular events. Biologic therapy for psoriasis has been found to be favorably associated with luminal coronary plaque, but it is unclear whether these associations are attributable to direct anti-inflammatory effects on the coronary arteries. Objective: To investigate the association of biologic therapy with coronary inflammation in patients with psoriasis using the perivascular fat attenuation index (FAI), a novel imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography (CCTA). Design, Setting, and Participants: This prospective cohort study performed from January 1, 2013, through March 31, 2019, analyzed changes in FAI in patients with moderate to severe psoriasis who underwent CCTA at baseline and at 1 year and were not receiving biologic psoriasis therapy at baseline. Exposures: Biologic therapy for psoriasis. Main Outcomes and Measures: Perivascular FAI mapping was performed based on an established method by a reader blinded to patient demographics, visit, and treatment status. Results: Of the 134 patients (mean [SD] age, 51.1 [12.1] years; 84 [62.5%] male), most had low cardiovascular risk by traditional risk scores (median 10-year Framingham Risk Score, 3% [interquartile range, 1%-7%]) and moderate to severe skin disease. Of these patients, 82 received biologic psoriasis therapy (anti-tumor necrosis factor α, anti-interleukin [IL] 12/23, or anti-IL-17) for 1 year, and 52 did not receive any biologic therapy and were given topical or light therapy (control group). At baseline, 46 patients (27 in the treated group and 19 in the untreated group) had a focal coronary atherosclerotic plaque. Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI -71.22 HU [interquartile range (IQR), -75.85 to -68.11 HU] at baseline vs -76.09 HU [IQR, -80.08 to -70.37 HU] at 1 year; P < .001) concurrent with skin disease improvement (median PASI, 7.7 [IQR, 3.2-12.5] at baseline vs 3.2 [IQR, 1.8-5.7] at 1 year; P < .001), whereas no change in FAI was noted in those not receiving biologic therapy (median FAI, -71.98 [IQR, -77.36 to -65.64] at baseline vs -72.66 [IQR, -78.21 to -67.44] at 1 year; P = .39). The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents, including anti-tumor necrosis factor α (median FAI, -71.25 [IQR, -75.86 to -66.89] at baseline vs -75.49 [IQR, -79.12 to -68.58] at 1 year; P < .001) and anti-IL-12/23 or anti-IL-17 therapy (median FAI, -71.18 [IQR, -75.85 to -68.80] at baseline vs -76.92 [IQR, -81.16 to -71.67] at 1 year; P < .001). Conclusions and Relevance: In this study, biologic therapy for moderate to severe psoriasis was associated with reduced coronary inflammation assessed by perivascular FAI. This finding suggests that perivascular FAI measured by CCTA may be used to track response to interventions for coronary artery disease.