Objectives: The localization of the reservoir fill port of Intrathecal Drug Delivery Devices (IDDS) can be difficult. The purpose of this study was to assess the ease of fill port access during the ultrasound-guided refill technique compared to the blind refill technique in IDDSs with a raised septum on the pump surface. Materials and Methods: Written informed consent was obtained from 19 adult patients undergoing regular refills of their Raised Septum IDDSs (RS-IDDSs). The primary outcome of this single center prospective comparison study was the number of attempts to enter the reservoir fill port with the needle comparing the ultrasound-guided technique vs. the blind technique. The number of skin punctures per refill procedure and time to enter the reservoir fill port was secondary outcomes. For between group comparisons the Friedman test for repeated measures on ranks was used. Results: One hundred and eleven refill procedures were assessed in 19 patients over a period of 24 months. The median number of attempts to enter the reservoir fill port with the needle differed significantly between the ultrasound-guided technique and the blind technique (4 [IQR: 1–6] vs. 1 [IQR: 1–3], p = 0.018), in favor of the blind technique. The median time to enter the reservoir fill port differed significantly between the ultrasound-guided technique and the blind technique (58 sec [IQR: 38–94] vs. 22 sec [IQR: 16–40], p < 0.001). Conclusions: The results of this study suggest that for a RS-IDDS the blind refill technique needs significantly less attempts to enter the reservoir fill port than the US-guided refill technique.