This study aimed to investigate the factors influencing the short-term and long-term efficacy of sclerotherapy for cystic thyroid nodules. Ninety-nine cystic thyroid nodules that underwent ultrasound-guided fine-needle aspiration biopsy, detection of thyroglobulin in fine needle aspirate (Tg-FNA), and ultrasound-guided percutaneous lauromacrogol injection were retrospectively enrolled from July 2018 to July 2021. All nodules were followed up at 3 and 12months after the procedure. Factors related to lauromacrogol injection efficacy, including initial volume, vascularity, pathological types, and Tg-FNA level, were analyzed. The nodules were classified as non-effective (VRR <50%) and effective groups (VRR ≥50%) at 3 months to evaluate short-term prognosis, and non-cured (VRR <90%) and cured groups (VRR ≥90%) at 12months to evaluate long-term prognosis. The volume of cystic thyroid nodules tended to shrink during follow-up. The resolution rate was 79.80% (79/99) at 3 months and 96.91% (94/97) at 12months. The cure rate was 80.41% (78/97) at 12months. Independent factors for the long-term prognosis included Tg-FNA level and vascularity (P < .05). Only Tg-FNA level was an independent factor for the short-term prognosis (P < .05). The area under the receiver operating characteristic curve for assessing the efficacy at 3 months was 0.79 (95% confidence interval [CI]: 0.65-0.89). With a cutoff value of Tg-FNA126.92 ng/mL, the specificity was 0.70, and the sensitivity was 0.85. Ultrasound-guided percutaneous lauromacrogol injection is an effective treatment option for cystic thyroid nodules. It is less effective in viscous or vascular predominantly cystic nodules.