OBJECTIVES This study aimed to compare the current 5 investigation strategies to defer cardiac testing in patients with stable chest pain. BACKGROUND For the clinical management of stable chest pain, the identification of patients unlikely to benefit from further cardiac testing is important, but the most appropriate investigation strategy is unknown. METHODS A total of 4,207 patients referred to coronary computed tomography angiography for stable chest pain were classified into low-and high-risk groups according to the 2016 National Institute of Health and Care Excellence (NICE) guideline-determined strategy; PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk tool-based strategy; 2019 European Society of Cardiology (ESC) guideline-determined strategy; and coronary artery calcium score (CACS), either in isolation (the CACS strategy) or as part of a weighted clinical likelihood model-based strategy (the CACS-CL strategy). The associations of obstructive coronary artery disease on coronary computed tomography angiography, major adverse cardiovascular events, and subsequent clinical management with risk groups according to different strategies were evaluated and compared. RESULTS The NICE, PROMISE, ESC, CACS, and CACS-CL strategies classified a proportion (22.63%, 29.21%, 41.84%, 46.76%, and 51.41%, respectively) of patients into low-risk groups. Compared with the NICE, PROMISE, ESC, and CACS strategies, the CACS-CL strategy had a stronger association between risk groups and obstructive coronary artery disease (odd ratios: 16.00 vs 2.93, 5.53, 7.94, and 10.39, respectively), major adverse cardiovascular events (HRs: 6.83 vs 1.90, 2.94, 4.23, and 5.13, respectively) and intensive subsequent clinical management as well as better metrics of diagnostic accuracy and positive net reclassification improvement. CONCLUSIONS Among contemporary strategies used to identify patients with stable chest pain at low risk, the use of CACS, especially when combined with clinical risk features, showed the strongest potential to effectively defer cardiac testing. (J Am Coll Cardiol Img 2022;15:91-104) (c) 2022 by the American College of Cardiology Foundation.