Many studies in research deal with optimizing emergency medical services (EMS) on both the operational and the strategic level. It is the purpose of this method-oriented article to explain the major features of “rule-based discrete event simulation” (rule-based DES), which we developed independently in Germany and Switzerland. Our rule-based DES addresses questions concerning the location and relocation of ambulances, dispatching and routing policies, and EMS interplay with other players in prehospital care. We highlight three typical use cases from a practitioner’s perspective and go into different countries’ peculiarities. We show how research results are applied to EMS and healthcare organizations to simulate and optimize specific regions in Germany and Switzerland with their strong federal structures. The rule-based DES serves as basis for decision support to improve regional emergency services’ efficiency without increasing cost. Finally, all simulation-based methods suggest normative solutions and optimize EMS’ performance within given healthcare system structures. We argue that interactions between EMS, emergency departments, and public healthcare agencies are crucial to further improving effectiveness, efficiency, and quality.