The study was to evaluate the safety and effectiveness of ultrasound-guided percutaneous laser ablation (pLA) as a nonsurgical treatment for primary parathyroid adenoma. Surgery was contraindicated in, or refused by, the included patients. No lesion enhancement on contrast-enhanced ultrasound immediately after pLA was considered "complete ablation." Nodule size, serum calcium, and parathyroid hormone level were compared before and after pLA. Complete ablation was achieved in all 21 patients with 1 (n = 20) or 2 (n = 1) sessions. Nodule volume decreased from 0.93 ± 0.58 mL at baseline to 0.53 ± 0.38 and 0.48 ± 0.34 mL at 6 and 12 months after pLA (P < 0.05). At 1 day, 6 months, and 12 months after pLA, serum PTH decreased from 15.23 ± 3.00 pmol/L at baseline to 7.41 ± 2.79, 6.95 ± 1.78, and 6.90 ± 1.46 pmol/L, serum calcium decreased from 3.77 ± 0.77 mmol/L at baseline to 2.50 ± 0.72, 2.41 ± 0.37, and 2.28 ± 0.26 mmol/L, respectively (P < 0.05). At 12 months, treatment success (normalization of PTH and serum calcium) was achieved in 81%. No serious complications were observed. Ultrasound-guided pLA with contrast-enhanced ultrasound is a viable alternative to surgery for primary parathyroid adenoma.