Abstract Aims Perivascular fat attenuation index (FAI) has emerged as a novel coronary computed tomography angiography (CCTA)–based biomarker predicting cardiovascular outcomes by capturing early coronary inflammation. It is currently unknown whether FAI adds prognostic value beyond that provided by single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and CCTA findings including coronary artery calcium scoring (CACS). Methods and results A total of 492 patients (mean age 62.5 ± 10.8 years) underwent clinically indicated multimodality CCTA and electrocardiography (ECG)-gated ^99mTc-tetrofosmin SPECT-MPI between May 2005 and December 2008 at our institution, and follow-up data on major adverse cardiovascular events (MACE) was obtained for 314 patients. FAI was obtained from CCTA images and was measured around the right coronary artery (FAI[RCA]), the left anterior descending artery (FAI[LAD]), and the left main coronary artery (FAI[LMCA]). During a median follow-up of 2.7 years, FAI[RCA] > − 70.1 was associated with an increased rate of MACE (log rank p = 0.049), while no such association was seen for FAI[LAD] or FAI[LMCA] (p = NS). A multivariate Cox regression model accounting for cardiovascular risk factors, CCTA and SPECT-MPI findings identified FAI[RCA] as an independent predictor of MACE (HR 2.733, 95% CI: 1.220–6.123, p = 0.015). However, FAI[RCA] was no longer a significant predictor of MACE after adding CACS (p = 0.279). A first-order interaction term consisting of sex and FAI[RCA] was significant in both models (HR 2.119, 95% CI: 1.218–3.686, p = 0.008; and HR 2.071, 95% CI: 1.111–3.861, p = 0.022). Conclusion FAI does not add incremental prognostic value beyond multimodality MPI/CCTA findings including CACS. The diagnostic value of FAI[RCA] is significantly biased by sex.