Liver transplantation is the most effective treatment for patients with end-stage liver failure, however infection after transplantation is a serious clinical complication. The purpose of this research was to investigate the molecular epidemiology and the influence of multidrug-resistant Gram-positive infection in patients, following liver transplantation, to provide reference for clinical treatment and prevention of Gram-positive bacterial infection.We isolated and detected bacteria from phlegm, throat swabs, urine, wound or wound secretions, blood, and fecal samples from 221 liver transplant patients in our hospital from January 2007 to April 2010. All isolated bacterial strains were identified and tested by minimal inhibitory concentration (MIC) drug-sensitive detection using the BioMerieux ATB bacterial identification instrument and repetitive extragenic palindromic-polymerase chain reaction (REP-PCR) detection of bacterial homology. Risk factors were calculated by multivariate Logistic regression analysis.We collected 250 specimens from 221 patients hospitalized following liver transplantation surgery, of which 29 patients developed multiple infections. Sixty-five Gram-positive bacterial strains were isolated from different specimens from 53 infectious patients. We detected 29 multidrug-resistant Gram-positive strains from 29 patients (44.62%), including 20 Staphylococcus aureus (S. aureus) strains (68.97%) and nine Enterococcus strains (31.03%). All 20 S. aureus strains were highly resistant to aminoglycosides (gentamicin), cephalosporins (cefoxitin), quinolones (ciprofloxacin and levofloxacin), lincomycins (clindamycin), penicillin, and erythromycin. The resistance rate reached 100% in some cases. The S. aureus strains were highly sensitive to vancomycin and oxazolidinone (linezolid), with MIC50 < 2 µg/ml for both. The nine Enterococci strains were also highly resistant to aminoglycosides, quinolones, and penicillins, and highly sensitive to vancomycin (MIC50 < 2 µg/ml) and oxazolidinone (MIC50 < 1 µg/ml). Using REP-PCR detection, S. aureus was divided into five genotypes with 14 B-type strains. Enterococcus was divided into 11 genotypes, with two D-type strains, two G-type strains, and two K-type strains. The risk factors for Gram-positive bacterial infection in patients following liver transplantation were preoperative use of antibiotics (OR = 3.949, P = 0.004), high intra-operative blood input (OR = 1.071, P = 0.005), and postoperative renal failure (OR = 5.427, P = 0.043).S. aureus and Enterococcus were the main pathogens causing infection following liver transplantation in patients with drug-resistant Gram-positive bacterial infection. The isolated strains were resistant to multiple antibiotics. B-type S. aureus strains were predominant. Reasonable use of antibiotics, decreasing intra-operative blood input, and preventing post-operative renal failure may reduce Gram-positive bacterial infections and the appearance of drug-resistant strains following liver transplantation.