Abstract: Evidence in animal intermediate hosts that susceptibility to larval infection with Echinococcus multilocularis is restricted to individual host factors prompted us to investigate the susceptibility markers in humans. Because antigens of the extracellular parasite E multilocularis are possibly presented by MHC molecules in a restricted way, we speculated that MHC polymorphism may influence resistance of the host towards infection and course of disease. We studied HLA‐A, ‐B, ‐DRB1, ‐DQB1 and ‐DPB1 polymorphism in 151 patients with alveolar echinococcosis. Patients with an observation period of more than 2 years were grouped according to the clinical follow‐up into cured (no recurrence following surgery) patients and patients with regressive or progressive forms of disease during benzimidazole chemotherapy. By comparing phenotypic frequency between patients with alveolar echinococcosis and healthy controls, HLA‐DRB1*11 was associated with a reduced risk for disease development (odds ratio=0.55, 95% confidence interval=0.34–0.88; P=0.01). HLA‐DQB1*O2 was more frequent in patients with progressive disease when compared with patients with regressive disease (54.3% vs 28.3%, P=0.02). The result suggests that HLA‐DRB1*11 might confer protection against alveolar echinococcosis and that HLA‐DQB1*02 may indicate a risk for progressive disease development. The findings may facilitate the search for immunodominant T‐cell epitopes of E. multilocularis.