Background-Sublingual immunotherapy (SLIT) has been deployed in humans and dogs; to the best of the authors' knowledge, there are no published studies about the use of SLIT in cats. Objectives-Evaluate the clinical efficacy of SLIT in atopic cats sensitized to dust and storage mites, assessing immunological changes associated with SLIT treatment. Animals-Twenty-two client-owned cats with clinical signs compatible with feline atopic dermatitis (fAD) and serum allergen-specific immunoglobulin (Ig)E against house dust and storage mites. Methods and materials-Prospective, multicentre, open-label clinical trial. Individualized mite-specific SLIT was administered orally for 12 months. All cats underwent clinical examination to record SCORing feline allergic dermatitis (SCORFAD), pruritus Visual Analog Scale (pVAS) and serum allergen-specific IgE and IgG, every three months for 12 months. Results-Sixteen of 22 cats (73%) completed the study and three of six cats withdrawn from the study were included in an intention-to-treat analysis. SCORFAD and pVAS values decreased significantly from baseline (T0) to the third month of treatment (P = 0.0004 and P = 0.0013, respectively), with median total values ranging from 19 (6-44) (T0) to 2.5 (0-17) (T12) (P = 0.0001), and from 8 (6-10) (T0) to 2.3 (0-8) (T12) (P = 0.0001), respectively. Allergen-specific IgE values decreased significantly from the ninth month (T9) of treatment (P = 0.0032), with median scores decreasing from 56 (12-729) (T0) to 34 (0-158) (T12) (P = 0.0208). No significant differences in allergen-specific IgG values were observed throughout the study. No adverse effects related to the use of SLIT were reported. Conclusions and clinical importance-Sublingual immunotherapy should be considered a rapid, effective, safe and well-tolerated treatment in cats with feline atopic dermatitis fAD.