SummaryHelminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL‐5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1‐mediated pathologies when the counterbalancing helminth‐induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2‐mediated responses in a household‐clustered randomized controlled trial in Indonesia. Total plasma IgE and whole‐blood IL‐5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three‐monthly single‐dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole‐ compared to placebo‐treated subjects. IL‐5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole‐treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B‐cell (IgE levels) and T‐cell (IL‐5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2‐mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases.