<i>Background:</i> There seems to be an association between paracetamol consumption during late pregnancy and the prevalence of wheezing in infancy and childhood. The aim of the present study is to determine whether the aforementioned association is modified by the presence of asthma in the mother. <i>Methods:</i> A total of 1,741 children aged 3–5 years from an epidemiological survey performed in the province of Murcia (Spain) were included in the analysis. Data on paracetamol consumption (never, at least once during pregnancy or at least once per month during pregnancy), wheezing symptoms in the offspring (according to the International Study of Asthma and Allergies in Childhood protocol) and the presence of asthma in the mother, together with other known risk factors for asthma, were obtained by means of a questionnaire. <i>Results:</i> The mean age of the children was 4.08 ± 0.8 years and 51.1% were males. The overall prevalence of current wheezing was 20.2%. The frequency of paracetamol usage was similar among asthmatic and non-asthmatic mothers, and only a small proportion of them took this drug at least once a month (13.8% of asthmatics and 11.0% of non-asthmatics). Compared to the mothers who never took paracetamol, there was a significant association between the mother having taken paracetamol at least once per month during pregnancy and the offspring suffering from wheezing at preschool age, but only among non-asthmatic mothers (odds ratio 1.94, 95% confidence interval 1.34–2.79 vs. odds ratio 1.05, 95% confidence interval 0.21–5.08). This association was maintained after controlling for potential confounders (odds ratio 1.74, 95% confidence interval 1.15–2.61). <i>Conclusions:</i> The frequent usage of paracetamol during pregnancy is associated with the prevalence of wheezing in offspring during preschool years. Asthma in the mother might modify this association.