ABSTRACT: The study was conducted in order to evaluate the effect of a fipronil/(S)-methoprene formulation against fleas on naturally infested cats. The study involved a population of 89 cats distributed among 24 veterinary practices in 9 regions of Spain. The product was applied according to label instructions on days 0, 30 and 60. Animals underwent parasitological and clinical assessments on day 0 and thereafter in monthly intervals (every 30 days) until day 90. Ctenocephalides felis was the most abundant species (98.9% of all fleas collected), and flea abundance on Day 0 was associated with the hair type, the location of the household, and the time elapsed from the last anti-flea treatment. Fipronil/(S)-methoprene demonstrated high efficacy and induced the reduction of clinical signs related to the presence of fleas. Clinical signs and flea abundance decreased significantly throughout time (P=0.001) with an efficacy rate of 72.6% at Day 30, 88.4% at Day 60 and 93.9% at Day 90. A high level of flea control and a remission of the clinical signs related to presence of fleas were observed on cats following 3 monthly applications a fipronil/(S)-methoprene formulation.