Background: Cytokine profile in patients with primary open-angle glaucoma (POAG) differs from that in healthy controls. Due to the different pathophysiological mechanisms involved in the genesis of primary congenital glaucoma (PCG) and POAG, it is possible that the cytokine profile could also differ. The main objective of this study was to compare the concentrations of cytokines in the aqueous humor of patients with PCG with those of POAG patients and a control group. Methods: A cross-sectional study was conducted. Aqueous humor samples were taken from PCG and POAG patients eligible for glaucoma or cataract surgery and from patients undergoing cataract surgery. Twenty-seven cytokines were analyzed using the Human Cytokine 27-Plex Immunoassay Kit (Bio-Rad Laboratories, Hercules, CA, USA). Results: A total of 107 subjects were included: patients with PCG (n= 19), patients with POAG (n= 54), and a control group (CG) of patients undergoing cataract surgery (n= 34). Most cytokines measured in aqueous humor in PCG presented decreased values compared with POAG and controls. A statistically significant difference was observed in IL-1ra, IL-2, IL-5, IL-7, IL-8, IL-10, IL-12, IL-15, IL-17A, Eotaxin, FGF basic, G-CSF, GM-CSF, IFN-γ, MIP-1α, PDGF-bb, MIP-1β, RANTES, TNF-α, and VEGF. Conclusion: PCG patients have a cytokine profile in aqueous humor different from POAG patients and patients without glaucoma, characterized by lower concentrations of multiple cytokines.