Over four consecutive harvests (2017-2020), the possibilities for organic cultivation of the Misket Vrachanski (susceptible) and Misket Kaylashki (resistant) varieties were studied in the region of Pleven, Central Northern Bulgaria. Two variants were grown in the experimental vineyards – with conventional and with organic methods of plant protection against the diseases downy mildew (Plasmopara viticola) and powdery mildew (Oidium, tuckeri). In both varieties, the damage to the leaves and clusters from the observed diseases was higher in the organic cultivation but that did not have a negative impact on the quantity and quality of the grape harvest. Misket Vrachanski showed greater susceptibility to downy mildew and powdery mildew in both cultivation practices. In Misket Kaylashki, the damage index was minimal. No significant difference was found in the rates of the studied indicators of the chemical composition of grapes from the organic and conventional cultivation. The differences due to the varietal specifics were more significant. The Misket Kaylashki variety exhibited higher sugar accumulation rates and titratable acidity in both variants. In the Misket Vrachanski wines, the conventional samples had higher extract and titratable acids, while the organic ones contained more total phenols. In the Misket Kaylashki wines, from both investigated variants, the amount of total extract, titratable acidity and phenolic components was similar, with the sugar-free extract being higher in the conventional samples. The organoleptic features of the experimental wines Misket Vrachanski and Misket Kaylashki, from the organic and conventional variants, were close, therefore the differences in their tasting ratings were insignificant.