AIM: In cases of symptomatic giant hepatic cysts, appropriate treatment is required to relieve symptoms. Ethanol, minocycline hydrochloride, and ethanolamine oleate have been conventionally used for ultrasound (US)-guided sclerotherapy. However, liquid sclerosing agents could mix with the residual fluid in the cyst and reduce their sclerotic effects. We carried out US-guided microfoam sclerotherapy using polidocanol for three patients and evaluated its efficacy and safety. METHODS: Between May 2016 and March 2017, three female patients with symptomatic giant hepatic cysts were referred to our hospital. All of them were prospectively included in this study. RESULTS: The maximum diameters of the hepatic cysts in the three patients were 92 × 89 × 86 mm, 155 × 119 × 140 mm, and 223 × 195 × 123 mm, respectively. Polidocanol microfoam was successfully administered through an 8.5-Fr pigtail catheter for all patients. One, two, and three microfoam sclerotherapy sessions were undertaken according to the initial cyst volume for cases 1, 2, and 3, respectively. The mean reduction rates of the cyst volume were 90.1% (85.5-98.9%) at 3 months, 96.3% (91.9-99.9%) at 6 months, and 99.5% (99.1-99.9%) at 9 months after treatment. No significant treatment-induced adverse effects were observed. CONCLUSION: Ultrasound-guided microfoam sclerotherapy using polidocanol could be an effective and safe method for the treatment of symptomatic giant liver cysts.