Staphylococcus aureus causes a wide range of illnesses, from skin infections and persistent bone infections to life-threatening septicemia and endocarditis. Methicillin-resistant S. aureus (MRSA) is one of the most common bacteria that cause nosocomial and community-acquired infections. Clindamycin is one of the most effective treatments for several bacterial infections. Despite this, these infections may develop inducible clindamycin resistance during treatment, leading to treatment failure. This study determined the incidence of inducible clindamycin resistance among S. aureus clinical isolates. A total of 800 S. aureus strains were identified from clinical samples collected from several university hospitals in Egypt. All isolates were examined for the presence of MRSA using cefoxitin (30 μg) and the Kirby Bauer disk diffusion technique. The induction phenotypes of all 800 S. aureus strains were evaluated using the disk approximation test (D test), as recommended by the Clinical and Laboratory Standard Institute. Of the 800 strains of S. aureus, 540 (67.5%) were identified as MRSA and 260 (32.5%) were classified as methicillin-sensitive S. aureus (MSSA). In MRSA infections, clindamycin constitutive and inducible resistance was more frequent than in MSSA infections (27.8% versus 11.5% and 38.9% versus 15.4%, respectively). Clindamycin-sensitive strains were more prevalent in MSSA (53.8%) than in MRSA (20.4%) infections. In conclusion, the frequency of constitutive and inducible clindamycin resistance in MRSA isolates emphasizes the need to use the D test in routine antimicrobial susceptibility testing to evaluate clindamycin susceptibility, as the inducible resistance phenotype can inhibit the action of clindamycin and thus affect treatment efficacy.