Objectives: Very preterm (VP, < 32 weeks gestation) birth and very low birth weight (VLBW, < 1500 g) are distinct but overlapping risk factors with different clinical implications. We aimed to investigate the separate and combined impacts of being born VP and/or VLBW on health-related quality of life in early and mid-adulthood. Methods: We analyzed data from the Dutch Project on Preterm and Small-for-gestational-age infants (POPS), a national prospective cohort of individuals born in 1983. Participants were categorized into three groups: (1) VP & VLBW, (2) VP-only, and (3) VLBW-only. We used the Health Utilities Index Mark 3 at ages 19 and 28, and the Short Form 6-Dimension at age 35 to assess multi-attribute utility (MAU) scores and domain-level functioning. Adjusted linear regression models were used, controlling for covariates and employing inverse probability weighting to account for attrition. Results: Overall MAU scores did not consistently differ between the exposure groups and the VP & VLBW reference group at any time point. However, specific domain-level differences emerged in early adulthood. At 19 years, the VLBW-only group reported significantly better speech functioning (β = 0.11, p = 0.01). At 28 years, the VP-only group had better hearing (β = 0.05, p = 0.04), while the VLBW-only group had worse ambulation (β = − 0.12, p < 0.01). By 35 years, these inter-group differences were no longer statistically significant. Female sex was a consistent predictor of poorer outcomes in several domains by age 35. Attrition-weighted models produced nearly identical results. Conclusions: VP and VLBW are not interchangeable risk categories. While overall HRQoL scores converged by mid-adulthood, distinct domain-specific and sex-based disparities were evident earlier in life. Our findings highlight the need for tailored interventions over a homogenous approach. Future research with consistent measures is required to confirm if this convergence persists over the life course.