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Background: Patients with chronic kidney disease, as a common disorder, usually necessitate the implementation of hemodialysis. Muscle cramps are one of the most disabling complications affecting their quality of life. Objectives: We aimed to investigate the efficacy of acupuncture as a safe alternative to the management of pain severity and frequency of calf cramps in dialysis patients compared to a control group. Methods: Fifty dialysis patients experiencing calf cramps who met the eligibility criteria were randomly allocated to two groups. Group A received routine management, including analgesic consumption, stretching exercises, and nine acupuncture sessions, including acupoints BL57, GV26, CV4, CV6, LV3, KI 1, LU7, LU9, and GB34. Group B underwent sham acupuncture therapy at locations other than the primary acupoints in addition to following the specified routine management. The pain severity was measured using the visual analog scale (VAS), and the daily frequency of calf cramps was evaluated at baseline and one month after treatment completion. Results: VAS scores and the frequency of calf cramps were improved one month after treatment completion in both groups. However, the improvement was significant in group A (p < 0.001), while it was not statistically significant in group B (p > 0.05). There was also a significant difference between both groups regarding reducing pain and the frequency of calf cramps, which showed the efficacy of acupuncture compared to the control group (p < 0.0001). Conclusion: Acupuncture can decrease pain and frequency of calf cramps in dialysis patients. [ABSTRACT FROM AUTHOR]