Purpose: About 20% of children with acute lymphoblastic leukemia (ALL) suffer from a relapse and only 1/3 of these can be cured.We aimed to compare the long-term health-related quality of life (HRQOL) of ALL survivors with and without a relapse. Method: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), we sent a questionnaire to all survivors of childhood ALL in Switzerland who had been diagnosed between 1976-2003 at an age of <16 years and who were currently aged older than 19 years. HRQOL was assessed with the SF-36 measuring 4 dimensions (scales) of physical health and 4 dimensions of mental health. A score of 50 corresponds to the mean of a healthy reference population. Results: From 396 ALL survivors eligible for the survey 318 (80%) participated until February 2009, but recruitment is still ongoing. Of these, 47 (15%) had had a relapse. Scores for all 8 domains were slightly higher in ALL survivors with and without relapse or similar compared to reference data from France and Germany (Swiss norm data unavailable). In five scales, scores did not differ between participants with and without relapse. Only in three scales (general health perceptions, role limitations due to physical health and vitality) scores in survivors with a relapse were slightly lower (48.4, 50.5 and 51.3 respectively) than in those without (53.8, 53.1 and 54.7 respectively; p¼0.001, 0.036 and 0.038). Conclusion: Although mortality in childhood ALL patients with a relapse is high, long-term HRQOL in those who survived is good, i.e. their HRQOL is comparable to both survivors without relapse and to the general population. The small differences found for three of eight scales will be further analyzed.