© 2022 Wolters Kluwer Health, Inc. All rights reserved.Objective This study aimed to evaluate the utility of computed tomography (CT) guidance in difficult lumbar puncture (LP) cases, which had a history of at least one unsuccessful blind attempt at LP (no imaging guidance), and to note potential advantages and disadvantages of the use of CT guidance. Methods In total, 32 CT-guided LP procedures performed between June 2019 and March 2021 were included. All LP indications were recorded. The procedures where the cerebrospinal fluid flow was provided by a single puncture were evaluated as "primary technical success.""Secondary technical success"corresponded with the procedures in which additional puncture was necessary for the cerebrospinal fluid flow. Results Intrathecal nusinersen injections due to spinal muscular atrophy constituted the largest procedure group of this study. Among 32 procedures, primary and secondary technical success rates were 78.12% and 28.57%, respectively. There were no major procedural complications. Conclusions Computed tomography-guided LP is an effective interventional technique offering an alternative approach in the setting of difficult LP procedures.