Gram-positive cocci are common causes of bloodstream and nosocomial infections, and their multi-drug resistance is an increasingly serious problem. The present study aimed to assess the prevalence of multi-drug-resistant Gram-positive cocci in a Chinese population. In this retrospective study, data about Gram-positive cocci from in-patients (January 2006 and December 2013) at the Second Hospital of Shanxi Medical University, Taiyuan, China, were reviewed. Antimicrobial susceptibility profile of the isolated Gram-positive cocci was evaluated using the disk diffusion method. Antibiotic resistance was determined according to the Clinical and Laboratory Standards Institute 2009 guidelines. The prevalence of drug resistance was determined, as well as correlation coefficients for various drugs between the resistance rate and year of sample collection. A total of 7789 Gram-positive cocci isolates were found, including 2576 (33%) coagulase-negative Staphylococci, 1477 (19%) Staphylococci aureus, 1343 (17%) Enterococcus faecalis, and 1139 (15%) Enterococcus faecium. The proportions of methicillin-resistant Staphylococci aureus (MRSA) and methicillin-resistant Staphylococci (MRS) were 31.5% (465/1477) and 61.6% (1587/2576), respectively. Among all isolates, MRS had much higher drug resistance rate than methicillin-sensitive Staphylococci (P<0.05). E. faecalis had a higher multi-drug resistance rate than E. faecium (P<0.01). Interestingly, MRSA resistance rates declined over the years, showing a negative correlation coefficient for all drugs, with significance for levofloxacin, azithromycin, erythromycin, and clindamycin (P<0.05), but not sulphamethoxazole/trimethoprim (P=0.057) and gentamicin (P=0.186). These results indicated that Staphylococci were the predominant Gram-positive cocci isolated. There was a trend of decreasing MRSA in the population studied.