Background: To compare the safety and accuracy of the 3D-printed operation guide template technique and the free-hand technique in the placement of the S2-alar-iliac (S2AI) screw. Methods: We conducted a retrospective analysis of 47 patients undergoing S2AI screw placement in our hospital, divided into the 3D-printed operation guide template group and the free-hand screw placement group. The duration of single S2AI screw placement was documented in all patients. A postoperative CT scan was performed to assess screw placement effectiveness according to the distance from the screw tip to the breach of the cortical bone wall. Results: In total, 42 screws were placed in the guide template group, with an average screw placement duration of 151.6 ± 44.8 s. Screw placement grading was as follows: 40 screws in grade 0, two in grade 1, and none in grades 2 and 3. This grading resulted in excellent and good rates of 95.2% and 100%, respectively. In total, 52 screws were placed in the free-hand group, with an average screw placement duration of 138.3 ± 45.9 s. Screw placement grading was as follows: 42 screws in grade 0, seven in grade 1, three in grade 2, and none in grade 3. This grading resulted in excellent, good and acceptable rates 80.8%, 94.2% and 100%, respectively. Screw placement duration did not significantly differ between the groups (p > 0.05). The excellent rate of screw placement was greater in the guide template group than in the free-hand group (p < 0.05), but the good and acceptable rates did not significantly differ between the two groups (p > 0.05). Conclusion: Both techniques can be applied to S2AI screw placement. The 3D-printed guide technique is superior to the free-hand technique in terms of safety and accuracy. © 2020, The Author(s).