Purpose <p>This study compared the outcomes of modified three-dimensional printed non-coplanar templates (3DPNCT) with those of conventional 3DPNCT for iodine-125 (¹²⁵I) seed implantation in malignant tumors and analyzed associated technical differences.</p> Material and methods <p>We analyzed patients with malignant tumors undergoing ¹²⁵I seed implantation in our department from February 2021 to May 2023. Cases using modified 3DPNCT guidance comprised the experimental group, while those using conventional 3DPNCT formed the control group. All patients underwent identical computed tomography (CT) scanning, preoperative planning, and 3D-printed template creation protocols. The experimental group featured modifiable guide posts enabling intraoperative needle angle/direction adjustments. Pre- and postoperative planning target volume (PTV) and dosimetric parameters included D₉₀, D₁₀₀, V₁₀₀, V₁₅₀, conformity index (CI), external index (EI), and homogeneity index (HI) were compared intra- and inter-group.</p> Results <p>A total of 70 patients were enrolled, including 35 in the experimental group and 35 in the control group. In the experimental group, pre- and post-operation values for PTV, D₁₀₀, CI and EI, were 61.4(24.9,106.6)cc and 61.6(24.9,106.7)cc, (71.9 ± 16.77) Gy and (65.6 ± 18.0)Gy, 0.7615(0.7102,0.7941) and 0.7780(0.7214,0.8172), 19.0(14.8,25.6)% and 16.1(13.0,28.0)%, respectively, showing a statistically significant difference (P &lt; 0.05). The PTV, D₉₀, D₁₀₀, V₁₅₀, CI, EI and HI values before and after the operation in the control group were (69.0 ± 55.0)cc and (69.1 ± 55.0)cc, (124.0 ± 12.4)Gy and (123.1 ± 12.6)Gy, (71.3 ± 13.7)Gy and (66.7 ± 13.5)Gy, (60.1 ± 7.5)% and (58.1 ± 7.8)%, (0.7296 ± 0.0702) and (0.7476 ± 0.0748), (24.6 ± 12.8)% and (21.8 ± 13.6)%, (34.4 ± 7.9)% and (36.5 ± 7.8)%, respectively, with a statistically significant difference. No statistically significant differences were observed in post-operative PTV and dosimetric parameters between the two groups except for D₉₀. For the experimental group, the median value of D₉₀ was 126.27&#xa0;Gy, and corresponding values were 121.63&#xa0;Gy for the control group (p &lt; 0.05).</p> Conclusions <p>The modified 3DPNCT improved consistency between pre- and post-operative dose parameters in comparison to the conventional 3DPNCT and showed the potential to deliver a higher dose to the tumor. This innovative 3DPNCT provides enhanced adaptability for intraoperative needle adjustments during seed implantation therapies.</p> Clinical trial number <p>Not applicable.</p>