PETHEMA (Programa Español de Tratamientos en Hematología, or, Spanish Program for Treatments in Haematology) a leading cooperative group in haematological research, has increasingly integrated real-world data (RWD) as a complement to traditional clinical trials. RWD research captures information from routine clinical practice, reflecting a broader patient population and enhancing external validity. PETHEMA has conducted impactful RWD studies in acute myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, and bone marrow failure syndromes, notably leveraging large clinical registries and molecular data. Despite challenges such as data heterogeneity, confounding factors, and regulatory constraints, RWD offers essential insights for personalised medicine. Future priorities include improving data interoperability, applying artificial intelligence, and rethinking legal frameworks to balance data protection with scientific progress. PETHEMA’s experience highlights the transformative role of RWD in supporting more informed and representative clinical decision-making in real-life haematology settings.