Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used for pain management, including after cesarean sections. Recently, it has been discovered that adding B vitamins (B1, B6, and B12) can help alleviate pain and inflammation, which is mediated by prostaglandin E2 (PGE2). This study aims to assess the effectiveness of adding B vitamins in reducing pain and PGE2 levels following a cesarean section. Methods: This study is a double-blind randomized clinical trial conducted at RSUP Wahidin Sudirohusodo and its affiliated teaching hospitals from April to June 2024. Patients were divided into two groups: an intervention group (receiving vitamins B1, B6, and B12 one hour before the surgical procedure) and a control group. Results: A total of 28 patients were evenly divided into two groups. At 4, 6, 8, 12, and 24 hours post-operation, the intervention group experienced a greater reduction in pain compared to the control group. Additionally, comparisons of PGE2 levels at 4 and 8 hours post-surgery revealed significant differences between the intervention and control groups, with lower PGE2 levels observed in the intervention group. Moreover, a significant correlation was found between pain levels and PGE2 levels in patients who underwent cesarean sections (p<0.05). Conclusion: The addition of B vitamins can reduce pain and PGE2 levels following a cesarean section.