The in vitro antifungal activity of luliconazole, a novel topical imidazole, against pathogenic fungi implicated in dermatomycoses was studied. A total of 91 clinical isolates, consisting of 59 Trichophyton rubrum isolates, 26 T. mentagrophytes isolates, 1 Epidermophyton floccosum isolate, and 5 Candida albicans isolates were tested by the broth microdilution method, employing lanoconazole, terbinafine, and bifonazole as reference drugs. The minimum inhibitory concentrations (MICs) of luliconazole against T. rubrum and T. mentagrophytes were in the range of 0.00012–0.004 μg/ml and 0.00024–0.002 μg/ml, respectively. The MIC90 of luliconazole for these two species of dermatophytes was the same, at 0.001 μg/ml, and these values were 4 times, 30 times, and more than 1000 times lower than those of lanoconazole, terbinafine, and bifonazole, respectively. Similarly, the 1 isolate of E. floccosum tested was inhibited by luliconazole with an MIC of 0.001 μg/ml. Luliconazole also proved to be very potent against C. albicans (MIC range, 0.031–0.25 μg/ml), nearly on par, in terms of efficacy, with lanoconazole (0.063–0.25 μg/ml) and more potent than terbinafine (2–>64 μg/ml) and bifonazole (0.5–4 μg/ml). These results showed that luliconazole was very potent in vitro against pathogenic fungi isolated from patients with dermatomycoses, and these findings emphasized the utility of luliconazole for the topical management of this condition.