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Diagnostic and treatment strategies for acute coronary syndrome have improved dramatically over the past few decades, but mortality and recurrent myocardial infarction rates remain high. An aging population with increasing co-morbidities heralds new clinical challenges. Therefore, in order to evaluate and improve current treatment strategies, detailed information on clinical presentation, treatment and follow-up in real-world patients is needed. The Future Optimal Research and Care Evaluation in patients with Acute Coronary Syndrome (FORCE-ACS) registry (ClinicalTrials.gov Identifier: NCT03823547) is a multi-center, prospective real-world registry of patients admitted with (suspected) acute coronary syndrome. Both non-interventional and interventional cardiac centers in different regions of the Netherlands are currently participating. Patients are treated according to local protocols, enabling the evaluation of different diagnostic and treatment strategies used in daily practice. Data collection is performed using electronic medical records and quality-of-life questionnaires, which are sent 1, 12, 24 and 36 months after initial admission. Major end points are all-cause mortality, myocardial infarction, stent thrombosis, stroke, revascularization and all bleeding requiring medical attention. Invasive therapy, antithrombotic therapy including patient-tailored strategies, such as the use of risk scores, pharmacogenetic guided antiplatelet therapy and patient reported outcome measures are monitored. The FORCE-ACS registry provides insight into numerous aspects of the (quality of) care for acute coronary syndrome patients.