An accelerated diagnostic protocol for evaluating low-risk patients with acute chest pain in a cardiologist-based chest pain unit (CPU) is widely employed today. However, limited data exist regarding the feasibility of such an algorithm for patients with a history of prior coronary artery disease (CAD). The aim of the current study was to assess the feasibility and safety of evaluating patients with a history of prior CAD using an accelerated diagnostic protocol. We evaluated 1,220 consecutive patients presenting with acute chest pain and hospitalized in our CPU. Patients were stratified according to whether they had a history of prior CAD or not. The primary composite outcome was defined as a composite of readmission due to chest pain, acute coronary syndrome, coronary revascularization, or death during a 60-day follow-up period. Overall, 268 (22%) patients had a history of prior CAD. Non-invasive evaluation was performed in 1,112 (91%) patients. While patients with a history of prior CAD had more comorbidities, the two study groups were similar regarding hospitalization rates (9% vs. 13%, p = 0.08), coronary angiography (13% vs. 11%, p = 0.41), and revascularization (6.5% vs. 5.7%, p = 0.8) performed during CPU evaluation. At 60-days the primary endpoint was observed in 12 (1.6%) and 6 (3.2%) patients without and with a history of prior CAD, respectively (p = 0.836). No mortalities were recorded. To conclude, Patients with a history of prior CAD can be expeditiously and safely evaluated using an accelerated diagnostic protocol in a CPU with outcomes not differing from patients without such a history.