BACKGROUND: Previous studies have indicated decreased health-related quality of life (HRQoL) shortly after kidney donation, returning to baseline in the longer term. However, a subgroup of donors experiences persistent HRQoL problems. To identify which HRQoL aspects are impacted most by the donation and to identify at-risk donors, more specific insight into psychosocial donation consequences is needed. METHODS: The current study examined the HRQoL course, donor-perceived consequences of donation for donors, recipients and donor-recipient relationships, and regret up to 12 months post-donation in donors from seven Dutch transplantation centres. Kidney donor candidates (n = 588) completed self-report questionnaires early in the screening procedure, of which 361 (61%) donated their kidney. RESULTS: Data for 230 donors (64%) with complete assessments before donation and 6 and 12 months post-donation were analysed. Results indicated that donor physical HRQoL was comparable at all time points, except for an increase in fatigue that lasted up to 12 months post-donation. Mental HRQoL decreased at 6 months post-donation, but returned to baseline at 12 months. Donors reported large improvements in recipient's functioning and a smaller influence of the recipient's kidney disease or transplantation on the donor's life over time. A subgroup experienced negative donation consequences with 14% experiencing regret 12 months post-donation. Predictors of regret were more negative health perceptions and worse social functioning 6 months post-donation. The strongest baseline predictors of higher fatigue levels after donation were more pre-donation fatigue, worse general physical functioning and a younger age. CONCLUSIONS: Future research should examine predictors of HRQoL after donation to improve screening and to provide potential interventions in at-risk donors.