Purpose Surgery is the cornerstone of craniosynostosis treatment. Two widely accepted techniques are described, endoscopy-assisted surgery (EAS), and open surgery (OS). In this study, we compare the perioperative and reconstructive outcome of EAS and OS in children ≤ 6 months of age treated at the Napoleón Franco Pareja Children's Hospital (Cartagena, Colombia). Methods According to the STROBE statement, retrospective enrollment of patients with defined criteria that underwent surgery to correct craniosynostosis between June 1996 and June 2022. Demographic data, perioperative outcomes, and follow-up was obtained from medical records. Student's t-tests were used for significance. Cronbach's alpha (α) was used to assess agreement between estimated blood loss (EBL). Spearman's correlation coefficient (rs) and determination coefficient (r2) were used to establish the association between the results of interest, and the Odds Ratio (OR) to calculate the risk ratio of transfusion of blood products. Results A total of 74 patients met the inclusion criteria, 24 (32.5%) belonged to the OS group and 50 (67.5%) to the EAS group. There was a high interobserver agreement quantifying the EBL. The EBL, transfusion of blood products, surgical time and hospital stay were shorter in EAS. Surgical time was positively correlated with EBL. There were no differences between the two groups in the percentage of cranial index (CrI) correction at 12 months of follow-up. Conclusion Surgical correction of craniosynostosis in children ≤ 6 months by EAS showed a significant decrease in EBL, transfusion requirements, surgical time and hospital stay compared to OS. Cosmetic results were similar in both groups.