Clinical pharmacology is a recent medical specialty that deals with everyday aspects of the relationship between drugs and humans, promoting safe and effective use of medicines while maintaining the sustainability of healthcare systems through pharmacoeconomics considerations. Since its creation in 2019, our Clinical Pharmacology Unit (UFC) has cooperated with the Pharmacy and Therapeutics Committee (CFT), creating, at request, technical and scientific reports that support decision processes of this local regulatory entity. As all clinical protocols need to be approved by CFT before institutional implementation, UFC acts as an expert and independent organ that evaluates clinical and pharmacological evidence, providing, ultimately, better healthcare access to patients. Our paper describes our cumulative experience and systematic approach in clinical protocol evaluation, over 4 years, with the use of a self-made checklist. We divided protocol evaluation into three sections: 1) introduction; 2) critical appraisal; and 3) final remarks and considerations. Since the most important part is critical appraisal, we further divided this section into two parts; the first one addresses formal aspects and the second discusses regulatory matters, pharmacology aspects, evidence-based prescription, safety concerns, and pharmacoeconomics considerations. We also describe key and fundamental aspects that, from our experience, should be included to grant protocol quality. Our experience, which derived from the evaluation of 63 protocols, showed that the suggestions emerging from the evaluation processes were well accepted by the proponent services and that the overall quality of the protocols was improved, resulting in better health services.