Background Antibiotic therapy directed against Propionibacterium acnes has been a mainstay of treatment in acne vulgaris for more than 40 years. Prolonged antibiotic usage has been associated with emergence of antibiotic-resistant P. acnes and is linked to treatment failure. Little work has been done in Malaysia on drug resistance in P. acnes and there is no surveillance data on this aspect to guide the clinical decision. Objective This study aims to evaluate antibiotic sensitivity of P. acnes isolated from patients with acne vulgaris in Kuala Lumpur Hospital, Malaysia. Methods This is a non interventional, single centered, cross-sectional hospital-based survey of antibiotic sensitivity of P. acnes isolated from patients with acne vulgaris in Kuala Lumpur Hospital from January 2010 to June 2010. Results A total of 100 patients were recruited in our study. P. acnes was isolated in 53% of patients and 11% had gram negative organism. Antibiotic resistant P. acnes was found in 15.1% of positive isolates. Clindamycin resistance was most common (15.1%) followed by erythromycin (7.5%), doxycycline (5.7%), tetracycline (1.9%) and minocycline (0%). Isolates of antibiotic resistant P. acnes was significantly higher in patients treated with antibiotics within the last 6 months (29%) as compared with non antibiotic treated patients (0%) (p<0.05). The mean duration of prior antibiotic treatment was significantly longer in the group of antibiotic resistant P. acnes as compared with antibiotic sensitive P. acnes (17.13 weeks vs 5.74 weeks, p<0.05). Conclusion Antibiotic resistant P. acnes is present locally with clindamycin and erythromycin conferring the highest resistance. Longer duration of antibiotic treatment predisposes to antibiotic resistant P. acnes and may also induce emergence of gram negative organisms. Strategies to reduce antibiotic resistance should be emphasized when prescribing antibiotic for acne vulgaris in order to achieve optimal therapeutic results while reducing the potential for antibiotic resistance.