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Objective. To compare effects of ultrasound- (US-) guided percutaneous electrolysis combined with an eccentric exercise program of the rotator cuff muscles in subacromial pain syndrome. Methods. Thirty-six patients were randomized and assigned into US-guided percutaneous electrolysis (n = 17) group or exercise (n = 19) group. Patients were asked to perform an eccentric exercise program of the rotator cuff muscles twice every day for 4 weeks. Participants assigned to US-guided percutaneous electrolysis group also received the application of galvanic current through acupuncture needle on each session once a week (total 4 sessions). Shoulder pain (NPRS) and disability (DASH) were assessed at baseline, after 2 sessions, and 1 week after the last session. Results. The ANOVA revealed significant Group∗Time interactions for shoulder pain and disability (all, P < 0.01): individuals receiving US-guided percutaneous electrolysis combined with the eccentric exercises experienced greater improvement than those receiving eccentric exercise alone. Conclusions. US-guided percutaneous electrolysis combined with eccentric exercises resulted in small better outcomes at short term compared to when only eccentric exercises were applied in subacromial pain syndrome. The effect was statistically and clinically significant for shoulder pain but below minimal clinical difference for function. Future studies should investigate the long-term effects and potential placebo effect of this intervention.