BACKGROUND: Patients with fibromyalgia experience chronic, widespread pain. It remains a misunderstood disorder with multimodal treatments providing mixed results. OBJECTIVES: To examine the effects of radial shockwave therapy (RSWT) compared to placebo on pain, pain catastrophizing, psychological indices, blood markers, and neuroimaging. Study-related experiences were also explored qualitatively. METHODS: Quantitative sensory testing (QST), Visual Analog Scale (VAS), Beighton Scoring Screen (BSS), Pain Catastrophizing Scale (PCS), blood biomarker (Interleukin (IL)-6 and IL-10), and brain fMRI were measured pre- and post-treatment along with a post-treatment survey. The RSWT group received five treatments (one week apart over five-week period) to the three most painful areas (500 shocks at 1.5 bar and 15 Hz, then 1000 shocks at 2 bar and 8 Hz, and finally 500 shocks at 1.5 bar and 15 Hz) versus sham treatment for the placebo group. RESULTS: There were no statistically significant differences in the BSS for hypermobility ( = .21;  = .74), PCS ( = .70;  = .22), VAS (;  = .20-.83) scores, QST for skin temperature and stimuli (;  = .25-.88), and for the pressure pain threshold (;  = .05-.21). The VAS scores had clinically significant changes (MCID greater than 13.90) with improved pain scores in the RSWT group. Neuroimaging scans revealed no cortical thickness changes. Post-treatment surveys revealed pain and symptom improvements and offered hope to individuals. CONCLUSION: RSWT was implemented safely, without any negative treatment effects reported, and acted as a pain modulator to reduce sensitivity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identification number NCT02760212.