This chapter presents an evidence-based framework for entrepreneurial decision-making based on the adoption of the scientific method for business decisions. It guides medical entrepreneurs through six sequential steps: identifying scenarios, defining actions, mapping their expected values, formulating testable hypotheses, conducting experiments, and making data-driven decisions. Using examples from real-life medical ventures—such as clinical trials, telehealth systems, and device competitiveness—the chapter demonstrates how hypotheses (e.g., adoption thresholds, efficacy rates) can be empirically tested to reduce uncertainty and bias. Because it combines quantitative approaches, pre-defined benchmarks, and continuous hypothesis testing, this approach transforms subjective entrepreneurial intuition into a rational, repeatable decision-making process that supports both pivoting and investment decisions.