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In the recent years, prolotherapy is increasingly being used in the field of musculoskeletal medicine. However, few studies have investigated its effectiveness in plantar fasciitis (PF). The purpose of this study was to compare the effectiveness of ultrasound-guided dextrose prolotherapy with radial extracorporeal shock wave therapy (ESWT) in the treatment of chronic PF. This randomized controlled trial was conducted on 59 patients with chronic PF. Patients were randomly assigned into two groups receiving three sessions of radial ESWT (29 patients) vs. two sessions of ultrasound-guided intrafascial 2 cc dextrose 20% injection (30 patients). The following outcome measures were assessed before and then six weeks and 12 weeks after the treatments: pain intensity by visual analog scale (VAS), daily life and exercise activities by Foot and Ankle Ability Measure (FAAM), and the plantar fascia thickness by ultrasonographic imaging. The VAS and FAAM scales showed significant improvements of pain and function in both study groups 6 weeks and 12 weeks after the treatments. A significant reduction was noted for plantar fascia thickness at these intervals (all p < .05). The inter-group comparison revealed that except for the FAAM-sport subscale which favored ESWT, the interaction effects of group and time were not significant for other outcome measures. Dextrose prolotherapy has comparable efficacy to radial ESWT in reducing pain, daily-life functional limitation, and plantar fascia thickness in patients with PF. No serious adverse effects were observed in either group. LEVEL OF EVIDENCE: Level I, randomized controlled trial., (Copyright © 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)