Abstract： Background::No convincing modalities have been shown to completely prevent postdural puncture headache (PDPH) after accidental dural puncture (ADP) during obstetric epidural procedures. We aimed to evaluate the role of epidural administration of hydroxyethyl starch (HES) in preventing PDPH following ADP, regarding the prophylactic efficacy and side effects.Methods::Between January 2019 and February 2021, patients with a recognized ADP during epidural procedures for labor or cesarean delivery were retrospectively reviewed to evaluate the prophylactic strategies for the development of PDPH at a single tertiary hospital. The development of PDPH, severity and duration of headache, adverse events associated with prophylactic strategies, and hospital length of stay postpartum were reported.Results::A total of 105 patients experiencing ADP received a re-sited epidural catheter. For PDPH prophylaxis, 46 patients solely received epidural analgesia, 25 patients were administered epidural HES on epidural analgesia, and 34 patients received two doses of epidural HES on and after epidural analgesia, respectively. A significant difference was observed in the incidence of PDPH across the groups (epidural analgesia alone, 31 [67.4%]; HES-Epidural analgesia, ten [40.0%]; HES-Epidural analgesia-HES, five [14.7%]; P <0.001). No neurologic deficits, including paresthesias and motor deficits related to prophylactic strategies, were reported from at least 2 months to up to more than 2 years after delivery. An overall backache rate related to HES administration was 10%. The multivariable regression analysis revealed that the HES-Epidural analgesia-HES strategy was significantly associated with reduced risk of PDPH following ADP (OR = 0.030, 95% confidence interval: 0.006-0.143; P < 0.001). Conclusions::The incorporated prophylactic strategy was associated with a great decrease in the risk of PDPH following obstetric ADP. This strategy consisted of re-siting an epidural catheter with continuous epidural analgesia and two doses of epidural HES, respectively, on and after epidural analgesia. The efficacy and safety profiles of this strategy have to be investigated further.