Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9–2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5–10 and 20–30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1–16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6–11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources.</p