To evaluate the targeting accuracy of a novel robot-assisted guidance technique relying on one pair of 2D C-arm images. In total, 160 punctures were carried out semi-automatically by using a novel robotic device. The needle's paths were planned based on one pair of 2D fluoroscopic images from different angles. Conically shaped aluminum tips inside a gelatin-filled plexiglass phantom served as targets. The accuracy of the needle placement was assessed by taking control CTs and measuring the Euclidean distance (ED) and normal distance (ND) between the needle and the target point. In addition, the procedural time per needle placement was evaluated. The accomplished mean NDs at the target for the 45°, 60°, 75° and 90° angles were 1.86 mm (SD ± 0.19), 2.68 mm (SD ± 0.18), 2.19 mm (SD ± 0.18) and 1.86 mm (SD ± 0.18), respectively. The corresponding mean EDs were 2.32 mm (SD ± 0.16), 2.68 mm (SD ± 0.18), 2.65 mm (SD ± 0.16) and 2.44 mm (SD ± 0.15). The mean duration of the total procedure, including image acquisition, trajectory planning and placement of four needles sequentially, was 12.7 min. Robotic guidance based on two 2D fluoroscopy images allows for the precise placement of needle-like instruments at the first attempt without the need for using an invasive dynamic reference frame. This novel approach seems to be a valuable tool for the precise targeting of various anatomical structures that can be identified in fluoroscopic images.