Spinal and epidural blocks are common practice in anesthesia and are usually used for various surgical or endoscopic procedures. Correct identification and puncture of the epidural or subarachnoid space determine the success or failure of the technique. Multiple attempts and difficult access to the epidural or subarachnoid space is a frequent problem in operating theaters and may be hazardous due to a number of possible acute or long-term complications. In addition, multiple punctures are associated with increased pain and patient discomfort. The aim of this study was to determine the factors associated with a difficult spinal or epidural block, dependent on the patient (age, gender, height, weight, body mass index, and quality of anatomical landmarks), the technique (type of blockade, needle gauge, and patient positioning), and the provider (level of experience). The study was conducted at the Department of Anesthesiology, Resuscitation, and Intensive Care Unit of University Hospital Osijek (Osijek, Croatia) and it included 316 patients who underwent a range of different surgical procedures in neuraxial blocks. There were 219 cases of first puncture success, while the overall success of neuraxial blocks was 97.5%. Five patients (1.6%) were submitted to the alternative technique, ie, general anesthesia. In three patients (0.9%), neuraxial block was partial so they required supplementation of intravenous anesthetics and analgesics. Furthermore, it was found that first puncture success was associated with younger age (P=0.007), lower weight (P=0.032), and body mass index (P=0.020). Spine deformity (P=0.015), poor identification of interspinous space (P=0.005), recumbent patient position during the puncture (P=0.001), and use of a paramedian approach were associated with first puncture failure. Adequate preoperative prediction of difficulties can help to reduce the incidence of multiple attempts, rendering the technique more acceptable and less risky to the patient, and consequently leading to improvement of medical care quality. The attending anesthesiologist should consider an alternative technique (general anesthesia or peripheral nerve block) for a patient if certain difficulties can be predicted.