Abstract Background It is important to know the impact of Very Preterm (VP) birth or Very Low Birth Weight (VLBW). The purpose of this study is to evaluate changes in Health-Related Quality of Life (HRQoL) of adults born VP or with a VLBW, between age 19 and age 28. Methods The 1983 nationwide Dutch Project On Preterm and Small for gestational age infants (POPS) cohort of 1338 VP (gestational age <32 weeks) or VLBW (<1500 g) infants, was contacted to complete online questionnaires at age 28. In total, 33.8% of eligible participants completed the Health Utilities Index (HUI3), the London Handicap Scale (LHS) and the WHOQoL-BREF. Multiple imputation was applied to correct for missing data and non-response. Results The mean HUI3 and LHS scores did not change significantly from age 19 to age 28. However, after multiple imputation, a significant, though not clinically relevant, increase of 0.02 on the overall HUI3 score was found. The mean HRQoL score measured with the HUI3 increased from 0.83 at age 19 to 0.85 at age 28. The lowest score on the WHOQoL was the psychological domain (74.4). Conclusions Overall, no important changes in HRQoL between age 19 and age 28 were found in the POPS cohort. Psychological and emotional problems stand out, from which recommendation for interventions could be derived.