ABSTRACT Tekirdağ köfte, a Turkish‐style meatball, is one of the most popular ground meat products in Turkey. The aim of this study was to evaluate the effect of different nisin and lactoferrin (Lf) concentrations and their combinations on the microbiological quality of Turkish‐style meatball (Tekirdağ köfte). For this purpose, the meatball dough was divided into six equal groups, and each of the groups was treated separately with different nisin and/or Lf concentrations (0, 100 and 200 µg/g). Analyses were performed on each meatball group at 0, 1, 3, 5, 7, 10 and 12 days for microbiological parameters (total mesophilic aerobic bacteria, lactic acid bacteria, coliforms, Escherichia coli, total staphylococcae, Staphylococcus aureus, total psychrophilic bacteria, Pseudomonas spp., sulfite‐reducing anaerobic bacteria, and yeast and mold) and physicochemical analyses (pH, water activity and moisture). Treatment with Lf alone and its combination with nisin significantly reduced (P < 0.05) the total aerobic bacteria, coliform, E. coli, total psychrophilic bacteria, Pseudomonas spp., and yeast and mold counts in meatballs. The largest reduction in these counts occurred on the meatballs treated with a mixture of Lf (200 µg/g) and nisin (100 µg/g). This combination prolonged the refrigerated shelf life of naturally contaminated Turkish‐style meatballs to 10 days compared to 3 days for nontreated control.PRACTICAL APPLICATIONSMeatballs are prepared from ground meat in Turkey. Studies have shown that total bacteria, coliform, and yeast and mold counts were usually high in meatball samples in Turkey, and these products were also usually contaminated with pathogenic bacteria. Therefore, this product mostly poses a risk to consumer health and has a short shelf life (about 3–4 days). In order to control the growth of spoilage microorganisms, the use of natural antimicrobial preservatives has been preferred in the food industry. For this purpose, nisin and lactoferrin were preferred in this study. Although there are many reports on the use of nisin to inhibit pathogenic bacteria, especially Listeria monocytogenes and Staphylococcus aureus in food, research on the antimicrobial activity of lactoferrin in food systems is limited.According to the results of our study, treatment with lactoferrin alone and its combination with nisin significantly reduced spoilage bacteria counts and extended the refrigerated shelf life of Turkish‐style meatballs. Therefore, the use of these natural compounds in meatballs may be useful for consumer health, and may also be a practical application for the producer because of the short shelf life of this product.