Rhinoviruses may be pathogens contributing to the development of childhood wheezing. However, their role in low risk infants without an asthmatic predisposition is unknown. Knowing which healthy, low risk children are at increased risk for childhood wheezing after rhinovirus wheezing illness (RV-WI) in infancy, might help in developing prevention and treatment strategies for childhood wheezing. The aim of this study was to determine the association of medically attended wheezing at the age of three with RV-WI in the first year of life in low risk children without parental asthma. In a low risk, prospective birth cohort study, we followed 181 healthy born children from birth through the third year of life. We considered children ‘low risk’ if neither parent had a doctor’s diagnosis of asthma. We determined infant RV-WI by parent-reported wheezing (based on daily logs) and simultaneous molecular rhinovirus detection in the first year of life. Respiratory function and blood eosinophil count were both measured in the first month of life. The primary outcome, third year wheezing, was defined as the use of prescribed inhaled asthma medications together with a doctor’s visit for respiratory symptoms in the third year of life. We calculated the association of RV-WI with medically attended third year wheezing and other known possible risk factors for wheezing at the age of three. Among low risk children, third year wheezing was observed in 7 out of 18 (39%) children with versus 10 out of 163 (6%) children without infant RV-WI (OR 9.7, 95% CI 3.1–33.5, P < 0.0001). The association between RV-WI and third year wheezing was unchanged after adjustment for potential confounders such as eosinophilia and atopic eczema. RV-WI is a robust and independent risk factor for third year wheezing in low risk children without parental asthma. Future research will identify and protect those children at increased risk for RV-WI.