INTRODUCTION: Post-dural puncture headache (PDPH) is a common complication following neuraxial anaesthesia that increases the duration of hospital stay. AIM: This study aims to evaluate the effectiveness of injection of the dexamethasone-lidocaine mixture in suboccipital muscles treatment of PDPH after cesarean section. PATIENT AND METHODS: A group of 90 females with PDPH following cesarean section under spinal anaesthesia were randomly allocated into two equal groups: study group (Group S) and control group (group C). All patients received bilateral intramuscular (in the suboccipital muscle) (Group S) (n = 45) patients received lidocaine 40 mg (2 mL of 2% solution) and dexamethasone 8mg in a total volume of 4 mL; whilst, patients in the control group (group C) (n = 45) received 4 mL normal saline. The primary outcome is the Visual Analogue Score for a headache at 24 hours after injection. RESULTS: Demographic data and the baseline, headache score, neck muscle spasm, and nausea were comparable in both groups. Group S showed lower headache score compared to group C at all the post-injection time points. All patients in group S showed resolution of nausea after the intervention; while none of the control group showed any improvement. All patients of group C needed rescue analgesia; while only 6 (13.3%) patients in group S asked for an analgesic. Time to the first analgesic request was longer in group S compared to group C (10.17 ± 7.96 hours versus 1.00 ± 0.00 hours, P < 0.001). CONCLUSION: Ultrasound-guided injection of the dexamethasone-lidocaine mixture in suboccipital muscles is effective management of PDPH after CS.