In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4–0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010–2014 vs. 38% in 2015–2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23–0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin’s disease (HR 0.1, 95% CI 0.1–0.3), multiple myeloma (HR 0.4, 95% CI 0.2–0.7) and solid tumors (HR 0.2, 95% CI 0.2–0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1–0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1–0.5), Hodgkin’s disease (HR 0.1, 95% CI 0.0–0.4), non-Hodgkin’s lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0–0.6), inborn diseases (HR 0.2, 95% CI 0.2–0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2–0.8).