Based on numerous archival sources, newspapers, and medical records, this paper discusses and analyses cholera epidemics in Dalmatia in the mid-19th century. The level of knowledge about the disease and the anti-epidemic measures has been considered, especially their effectiveness and topicality in view of the existing and growing discussions about the aetiology of diseases. In the second part of the paper, the cholera epidemic in Zadar in 1849 has been analysed as a case study. Records of cholera in the registers of deaths in Zadar allow us to estimate the number and age, gender, and social structure of deaths. The epidemic lasted three months and took 62 lives. It affected both men and women, and all age groups, especially the fertile one. Given the aetiology of the disease, the most endangered and most severely affected by the epidemic were the individuals of lower social and financial status, whose living and business conditions favoured a faster, stronger, and more intensive development of the disease.