Introduction: Emergent technologies, i.e., monopolar capacitive coupled Radiofrequency (mcRF) and Platelet Rich Plasma (PRP) are now available to treat conditions characterized by a failed Wound Healing Response. Both mcRF and PRP positively influence the chemical/cellular inflammatory cascade to promote healing. mcRF application results in temperature elevation at the targeted structure up to 50℃ stimulating heat shock proteins, thus inciting the Wound Healing Response. Ultrasound-guided PRP injections results in an inflammatory/reparative reaction through cytokinin release. Methods: Sixty-eight patients who have failed previous conservative treatment for tendinopathies and chronic ligament conditions of the elbow, hip, knee and ankle/foot, were treated either with mcRF or PRP. Treatments were delivered directly by the investigator, and patients were followed prospectively for an average of 19.7 months (range 15 to 24 months). Results: Average age for the mcRF cohort was 53 years (range 17 to 88). Average age for the PRP group was 58 (range 19 to 90). The male to female ratio for both groups was 1/1. 33 of 42 patients treated with mcRF experienced marked improvement (78%), while in the PRP group 19 of 26 patients experienced marked improvement (73%) as self-assessed by study subjects. Discussion/Conclusion: Results of this study are in agreement with reports on the use of both technologies; however, this is the first time that a side-by-side comparison is established. PRP and mcRF represent a new approach to musculoskeletal pathology; both modalities aim at inducing a biological response and are considered at the frontier of regenerative therapeutics. The high safety profile suggests that these, non-invasive (mcRF) and minimally invasive (PRP), office-based alternatives for the management of musculoskeletal conditions are valuable tools and should be used in accordance with a clear understanding of the underlying pathology.