In a prospective-longitudinal study, prevalence rates of otitis media with effusion (OME) were analysed in 150 healthy-born and 100 high-risk-born infants, aged 0-2 years. In order to determine OME, otoscopy and tympanometry were performed at 3-monthly intervals beginning at term date. The Maastricht Otitis Media with Effusion Study (MOMES) algorithm was used to standardize the diagnosis. The distribution of relevant background characteristics was similar in both groups except for gestational age and birth weight, which were significantly lower (P < 0.001) in the high-risk-born group. The ratio of unilateral:bilateral OME was 2:3. Prevalence rates of OME were strongly associated with age (P < 0.001). During the first months of life, OME prevalence rates increased rapidly in both groups, but did not differ significantly. However, from the age of 6 months on, OME prevalence rates of the high-risk group became significantly higher compared with the normal group (P < 0.05). The peak prevalence of OME (59% in the high-risk group versus 49% in the normal group) was observed around the age of 10 months. Although gradually decreasing prevalence rates were noted in both groups with aging, the differences between high-risk and normal infants remained, at least up to 24 months. In conclusion, OME is a very prevalent, age-dependent disorder during infancy, especially in high-risk infants. Peak prevalence of OME was found in the second half of the first year of life.