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The selection of starter cultures with different technological profiles and suitable microclimatic conditions is among the main tools used to improve the technological quality and safety of dry-cured salami. The aim of this study is to evaluate the effect of two different starter cultures [fast (SR) and medium (SM) acidification] during the process and on the quality of typical Italian dry-cured "Salame Napoli". The ripening process was evaluated in dry-cured salami made with different cultures: Euroferment Medium (Staphylococcus xylosus, Lactobacillus plantarum) in SM and Euroferment Rapid (Staphylococcus carnosus, Staphylococcus xylosus, Lactobacillus sakei) in SR. The salami was stuffed in artificial casings, dried for 5 days and then ripened for 28 days at a controlled temperature of 12–14 °C and 80–90% RH. During the ripening process, an evaluation of the appearance, the pH, and the weight loss of the salami were conducted. For each finished product, the physical–chemical, microbiological, rheological, and sensory characteristics were evaluated. The results showed that the different starter cultures influenced the pH descent, which was faster in SR, reaching a pH value of 4.80 in three days. This influenced the consistency profile of the SR salami, which showed higher hardness (46.04 ± 6.53 in SR vs. 35.60 ± 2.62 in SM; p < 0.05) and gumminess (19.21 ± 3.44 in SR vs. 11.89 ± 0.71 in SM; p < 0.05) values. SR salami revealed a higher count of yeasts and a lower malondialdehyde concentration than SM. The presence of the starter in SM has positively affected the intensity of the aroma. The outcomes indicated the importance of selecting starter cultures to not only ensure food safety but also to obtain the desired sensorial characteristics of the product. [ABSTRACT FROM AUTHOR]