Objective: To evaluate the treatment safety and efficacy of iodine 125 (I-125) seeds implantation in patients with bone metastases and assess the availability of quality of life (QOL) as an index for efficacy evaluation. Patients and Methods: The study enrolled 98 patients with 133 bone metastases from July 2010 to January 2016, who had undergone computed tomography-guided brachytherapy with I-125 seeds. Brief pain inventory was administered to assess the degree of pain at the preoperative (W0) and postoperative 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 24 weeks (W2, W4, W8, W12, and W24). Drug use, QOL score, and complications were also assessed. Results: Postoperative pain scores were significantly decreased and maintained for a long term. Numerical rating scale score at W0 was 7.3 +/- 1.6, which was decreased to 4.5 +/- 1.7 (P < 0.01), 3.7 +/- 1.3 (P < 0.01), 2.5 +/- 1.1 (P < 0.01), 1.9 +/- 0.9 (P < 0.01), and 1.3 +/- 0.5 (P < 0.01) at W2, W4, W8, W12, and W24, respectively. After standardized transformation, the dose of morphine for patients at W0 was 175.2 +/- 24.5 mg, which was decreased to 91.2 +/- 21.7 mg (P < 0.01), 89.4 +/- 24.6 mg (P < 0.01), 89.4 +/- 24.6 mg (P < 0.01), 72.8 +/- 14.8 mg (P < 0.01), and 56.7 +/- 11.3 mg (P < 0.01) at W2, W4, W8, W12, and W24, respectively. The efficiency reached 65.3%, 85.1%, 91.2%, 95.2%, and 92.7% at postoperative W2, W4, W8, W12, and W24, respectively. QOL score at W0 was 17.4 +/- 3.3, which increased to 23.2 +/- 4.5 (P < 0.01), 28.6 +/- 7.6 (P < 0.01), 43.2 +/- 9.1 (P < 0.01), 45.6 +/- 10.3 (P < 0.01), and 47.6 +/- 9.8 (P < 0.01) at W2, W4, W8, W12, and W24, respectively. Conclusion: Brachytherapy with I125 seeds was safe and effective for treating bone metastases, offering a potential alternative to external-beam radiotherapy. QOL could be applied to evaluate the efficacy of I-125 seeds implantation for treating bone metastases.