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Abstract Purpose Rare diseases (RD) produce an important public health impact, but their specific morbimortality burden remains unknown. Based on Death Certificates (1997–2017), the secular trend (ST) and spatial distribution of deaths due to RD are analyzed. Methods The ICD-10 classified Death Certificates were obtained from the Ministry of Health. A Python web scraper was developed to query the orpha.net web catalogue to establish a correspondence between Orpha and ICD-10 codes. The RDs mortality rate per 1,000 deaths (RD*1000) was calculated by sex, age groups, and by ICD-10 chapters for the five regions of Argentina (Northwest, Northeast, Centro, Cuyo, and Patagonia), as well as for its 24 provinces and 513 departments. Secular trend (ST) was analyzed using Joinpoint software, while spatiality was assessed through Moran’s and LISA indices. Results The RD*1000 death rate at country level was 189.4. Patagonia exhibited the highest rate, followed by Cuyo, Centro, Northeast and Northwest, being these conditions higher in women. The ST was negative between 1997 and 2009 and positive between 2009 and 2017. The geographical distribution of the clusters exhibiting high and low rates was mainly observed in the central and northern regions of the country, respectively. According to ICD-10, the prevalent categories were neoplasms, followed by eye diseases, congenital malformations, diseases of the nervous and digestive systems and diseases of the blood. Conclusion The geographical distribution of RD deaths in Argentina exhibits significant heterogeneity, characterized by a latitudinal arrangement. This phenomenon can be attributed to socioeconomic inequalities, intricately linked to population dynamics and migratory patterns. Clinical trial registration Not applicable. This study involved the analysis of secondary data and did not require clinical trial registration.