Background. The aim of the study was to access Health Related Quality of Life (HRQoL) in preschool cancer survivors during the first 3 years of continuous remission after the end of successful treatment, and to identify predictors of HRQoL. Procedure. Parent-reported HRQoL was assessed in 53 preschool children treated successfully for cancer, using the TAPQOL and compared with norm data. Longitudinal mixed models analyses were performed to investigate to what extent demographic and medical variables and parental psychological distress were predictive of HRQoL over time. Results. Two months after the end of successful cancer treatment, survivors showed significantly (P < 0.01) more problem behavior and anxiety, and scored significantly worse (P < 0.01) on sleeping, motor functioning, positive mood and liveliness than the norm. One year after the end of treatment survivors still showed significantly (P < 0.01) more anxiety and worse motor functioning. The level of HRQoL in survivors had normalized 2 and 3 years after the end of treatment. Longer duration of treatment, bad prognosis and greater parental psychological distress were associated with worse scores on the Physical Component Score of the TAPQOL. Medical variables and parental psychological distress were not associated with the Mental Component Score. Conclusions. Survivors adjusted well to the cancer experience and HRQoL improved with time. Despite overall resilience in survivors over time, physical as well as psychosocial monitoring in follow-up is recommended. Standard aftercare should preferably include psychosocial screening, education, and counseling directed at both survivors and parents.