No clear consensus exists on how to best prevent severe headache from occurring after accidental dural puncture. We conducted a quantitative systematic review to identify all available evidence for the prevention of postdural puncture headache (PDPH) and included 17 studies with 1264 patients investigating prophylactic epidural blood patch (PEBP), epidural morphine, intrathecal catheters, and epidural or intrathecal saline. The relative risk (RR) for headache after PEBP was 0.48 [95% confidence interval (CI): 0.23-0.99] in five non-randomized controlled trials (non-RCTs) and 0.32 (0.10-1.03) in four randomized controlled trials (RCTs). The RR for epidural morphine (based on a single RCT) was 0.25 (0.08-0.78). All other interventions were based on non-RCTs and failed statistical significance, including long-term intrathecal catheters with an RR of 0.21 (0.02-2.65). There are a number of promising options to prevent PDPH, yet heterogeneity between the studies and publication bias towards small non-RCTs with positive results limits the available evidence. Thus, a large multicentre RCT is needed to determine the best preventative practices.