Recent feedback from physical activity (PA) participants, fitness professionals, and physicians has indicated that there are limitations to the utility and effectiveness of the existing PAR-Q and PARmed-X screening tools for PA participation. The aim of this study was to have authorities in exercise and chronic disease management to work with an expert panel to increase the effectiveness of clearance for PA participation using an evidence-based consensus approach and the well-established Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument. Systematic reviews were conducted to develop a new PA clearance protocol involving risk stratification and a decision-tree process. Evidence-based support was sought for enabling qualified exercise professionals to have a direct role in the PA participation clearance process. The PAR-Q+ was developed to use formalized probes to clarify problematic responses and to explore issues arising from currently diagnosed chronic disease or condition. The original PARmed-X tool is replaced with an interactive computer program (ePARmed-X+) to clear prospective PA participants for either unrestricted or supervised PA or to direct them to obtain medical clearance. Evidence-based validation was also provided for the direct role of highly qualified university-educated exercise professionals in the PA clearance process. The risks associated with exercise during pregnancy were also evaluated. The systematic review and consensus process, conforming to the AGREE Instrument, has provided a sound evidence base for enhanced effectiveness of the clearance process for PA participation of both asymptomatic populations and persons with chronic diseases or conditions.