Randomized controlled trials (RCTs) are considered one of the highest level of evidence in clinical practice, due to their strong confidence and robustness in producing data. The “randomization” (e.g., allocating patients randomly in each group of the study) allows eliminating many pre-analytical differences that might bias the entire study. Nevertheless, RCTs aren’t free of internal pitfalls that might make them not easy to be developed or utilized. Our objective is to explain RCT management difficulties and suggest certain tips useful for the design of a RCT in thoracic disease domain. In particular have a realistic timeline, define a clear objective and precise endpoints, balance the study with a correct randomization and focus on the right equilibrium between strict selection criteria and more heterogeneous parameters are key elements that help researchers assuring a strong scientific validity.