Respiratory virus infections cause a significant number of hospitalization and deaths globally. This study investigated the association between single and multiple respiratory virus infections and risk of admission to a general ward, intensive care unit or death in patients aged 0-105 years (mean +/- s.d. = 24.4 +/- 24.1 years), from North West England, that were tested for respiratory virus infections between January 2007 and June 2012. The majority of infections were in children aged 5 years. Dual or multiple infections occurred in 10.4% (1214/11 715) of patients, whereas single infection occurred in 89.6% (10 501/11 715). Rhinovirus was the most common co-infecting virus (occurring in 69.5%; 844/1214 of co-infections). In a multivariate logistic regression model, multiple infections were associated with an increased risk of admission to a general ward [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.2-1.7, P < 0.0001]. On the other hand, patients with respiratory syncytial virus (RSV) and human parainfluenza virus types 1-3 (hPIV1-3), as a single infection, had a higher risk of being admitted to a general ward (OR 1.49, 95% CI 1.28-1.73, P < 0.0001 and OR 1.34, 95% CI 1.003-1.8, P = 0.05, respectively); admitted to an intensive-care unit or dying (OR 1.5, 95% CI 1.20-2.0, P = 0.001 and OR 1.60, 95% CI 1.02-2.40, P = 0.04, respectively). This result emphasizes the importance of RSV, hPIV and mixed infections and calls for research on vaccines, drugs and diagnostic tests targeting these respiratory viruses.