Myotonic Dystrophy type 1 (DM1) is a genetic disease with a broad clinical spectrum. Cardiac involvement is common and it is one of the main cause of mortality and morbidity. Current preclinical models fail to entangle the complexity of the disease. In order to overcome such limitations we wanted to explore the use of organoids – complex in vitro models that replicate organ morphology and physiology – to replicate the pathogenic hallmarks of DM1. Four iPSCs lines harbouring a wide range of CTG expansions on DMPK gene were obtained from National Institute of Neurological Disease and Stroke. Following an established protocol, we generated patient-derived cardiac Organoids (PdOs). PdOs were analyzed at morphological, molecular and functional level and compared to organoids generated from healthy iPSCs (controls). Compared to controls, we observed statistically significant differences in PdOs regarding morphology (PdOs were hypertrophic), beating rates (lower beating rates), tight junction protein expression (Zonula Occludens 1) and gene expression regarding COL1A1, INSR, IGFR, CACNA1C. Moreover, PdOs showed altered calcium transients with a slower decline in intracellular calcium concentration during the cardiac cycle. No differences were found regarding sarcomeric structure or mitochondrial morphology (Mito-Tracker, Thermofisher). In conclusion, we were able to generate patient-derived cardiac organoids that mimic some of the known feature occurring in vivo. These platform may serve to further enlighten the complexity of the disease and as a tool to drug testing. LF would like to thank “Fondazione Un Passo per Te – per la ricerca nelle malattie neuromuscolari”