Background: Individuals with atopic conditions may have increased susceptibility to infections outside the organs directly affected by their atopic condition. Objective: We tested the hypothesis that atopic conditions overall, and stratified by smoking history, are associated with increased risk of hospitalization for infections. Methods: We collected information on smoking history and self-reported atopic conditions from 105 519 individuals from the general population and followed them for up to 23 years for infectious disease hospitalizations and deaths. For asthma, we focused on never smokers with asthma diagnosed before age 50 (early asthma) to minimize confounding by chronic obstructive pulmonary disease. Results: During follow-up, 11 160 individuals had infections. Never smokers with early asthma versus no atopic conditions had significantly increased risks of any infection (hazard ratio 1.65; 95% confidence interval 1.40–1.94), pneumonia (2.44; 1.92–3.11) and any non-respiratory tract infection (1.36; 1.11–1.67); results were similar in ever smokers. Never smokers with any asthma had significantly increased risks of any infection (1.44; 1.24–1.66) and pneumonia (1.99; 1.62–2.44). Neither atopic dermatitis (1.00; 0.91–1.10) nor hay fever (1.00; 0.93–1.07) was associated with risk of any infection. In never smokers, risk estimates for any infection were comparable between asthma and diabetes, as were the population attributable fractions of 2.2% for any asthma and 2.9% for diabetes. Conclusion: Early asthma was associated with significantly increased risks of any infection, pneumonia and any non-respiratory tract infection in never and ever smokers. In never smokers, risk estimates as well as population attributable fractions for any infection were comparable between asthma and diabetes, suggesting that asthma may be a substantial risk factor for infections in the general population.