Updated project metadata. Parasitic nematodes of humans, animals and plants cause significant economic losses worldwide. Control of these pathogens is currently challenging due to the widespread problem of nematode anthelmintic resistance. Unfortunately, most efforts to develop anti-nematode vaccines for use in animals and humans have not succeeded. However, one effective (dead) anti-nematode vaccine (Barbervax) has been developed to protect livestock animals against the socioeconomically important parasitic nematode Haemonchus contortus (barber’s pole worm). This vaccine contains a major native antigen, termed H11. In its native form, H11 alone consistently induces high immunoprotection (75-95%) in animals, but recombinant forms thereof do not. Here, to test the hypothesis that post-translation modification of H11 is responsible for achieving the immunoprotection. We explored the N-glycoproteome and N-glycome of H11 using high-resolution mass spectrometry and assessed the roles of N-glycosylation in protective immunity against H. contortus. We demonstrated that N-glycans are a predominant protective component that induces protection and an associated IgG antibody response in immunised animals. We also showed that anti-H11 IgG antibodies confer specific, passive immunity in naïve animals. This study is the first detailed investigation of the relevance of protein glycosylation in protective immunity against a parasitic nematode, and should have important implications for developing vaccines against metazoan parasites.