Background: Propionibacterium acnes (P. acnes) has been implicated in the pathogenesis of acne vulgaris since the beginning of the last century. Over several decades, topical and systemic antibiotics have been the main line of treatment for acne vulgaris. However, in the present era of increased antibiotic usage, resistant strains have emerged. Objectives: The aim of this study is to determine the antibiotic resistance pattern of P. acnes isolated from patients with acne vulgaris at the dermatology clinics of Kasr Al-Ainy teaching Hospital. Methodology: Specimens from 100 patients with acne vulgaris were extracted from the pustules, taken by sterile cotton swabs and transported by thioglycolate media. Each swab was inoculated onto two blood agar plates, one incubated aerobically at 37ºC for 24h and the other anaerobically for one week. P. acnes was identified by Gram stain and biochemical tests. Their sensitivity to doxycycline, erythromycin, clindamycin, tetracycline, azithromycin and trimethoprim-sulfamethoxazole was determined on Muller Hinton media by disc diffusion method. Results were interpreted according to the National Committee for Clinical Laboratory Standards (NCCLS) guidelines. Results: A total of 44 P. acnes isolates were identified from 100 patients with acne vulgaris, out of which 22.7% were resistant to clindamycin, 11.4% were resistant to trimethoprim-sulfamethoxazole and 9% were resistant to erythromycin. Resistance to doxycycline, tetracycline or azithromycin was not detected. Trimethoprim-sulfamethoxazole showed statistically significant difference in the resistance pattern compared to patient's sex (p = 0.029) and to receiving previous treatment (p = 0.018). Conclusion: P. acnes is prevalent in patients with acne vulgaris (44%) and resistant strains are detected especially in those who have received previous therapy for more than 2 weeks (68%). It is recommended that dermatologists and family physicians follow the guidelines for proper management of acne, with the judicious use of antibiotics, in order to prevent antibiotic resistance.