Abstract Background The aim of the study was to investigate long-term risk and spectrum of subsequent neoplasm (SN) in childhood cancer survivors and to identify how trends in therapy influenced cumulative incidence of SN. Patients and methods The population-based cohort comprises 3271 childhood cancer patients diagnosed in Slovenia aged ≤ 18 years between 1st January 1961 and 31st December 2013 with a follow-up through 31st December 2018. Main outcome measures are standardised incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of SN. Results After median follow-up time of 21.5 years for 5-year survivors, 230 patients experienced 273 SN, including 183 subsequent malignant neoplasm (SMN), 34 meningiomas and 56 nonmelanoma skin cancers. 10.5% patients received radiotherapy only, 31% chemotherapy only, 26.9% a combination of chemotherapy and radiotherapy and 16.1% surgery only. The overall SIR was almost 3 times more than expected (SIR 2.9), with survivors still at 2-fold increased risk after attained age 50 years. The observed cumulative incidence of SMN at 30-year after diagnosis was significantly lower for those diagnosed in 1960s, compared with the 1970s and the 1980s (P heterogeneity < 0.001). Despite reduced use of radiotherapy over time, the difference in cumulative incidence for the first 15 years after diagnosis was not significant for patients treated before or after 1995 (p = 0.11). Conclusions Risks of developing a SMN in this study are similar to other European population-based cohorts. The intensity of treatment peaked later and use of radiotherapy declined slower compared to high income countries, making continuous surveillance even more important in the future.