The Lazaretto, an institution where travelers and goods were accommodated for protection against infectious diseases, played an important role for the Dalmatian cities of Dubrovnik and Split in the Early Modern Period. The primary function of the Lazaretto was health, but the secondary, trading function was equally important. The first chapter of the paper focuses on the background that led to the creation of the Lazaretto, that is the appearance of the plague epidemic, and the characteristics of the Lazaretto in the European context. The next part of the paper focuses on Dubrovnik, which, in order to protect itself from the epidemic and enable further commercial development, was the first to establish quarantine in 1377. It shows the establishment of the Lazaretto, life inside the Lazaretto at Ploče, the services that were responsible for a successful trade and the fight against epidemics, and finally a brief overview of the situation from the fall of the Republic of Dubrovnik to present day. The next part of the paper deals with the description of the Split Lazaretto, which became the main Venetian point for trade with the Ottoman Empire. It describes its establishment, appearance and functioning, important services, and finally the repurposing of the role and the demolition of the Lazaretto. With the establishment of the Lazaretto, Split experienced rapid development, but it also became a major competitor to the Dubrovnik Lazaretto, which led to conflicts between the Venetians and the Ragusans for supremacy over trade, and their relations are the subject of the last part of this paper.