We describe trends in incidence rates of methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected and HIV-uninfected patients enrolled in a large northern California Health Plan, and the ratio of MRSA to methicillin-susceptible S. aureus (MSSA) case counts. Between 1995 and 2010, 1549 MRSA infections were diagnosed in 14060 HIV-infected patients (11·0%) compared to 89546 MRSA infections in 6597396 HIV-uninfected patients (1·4%) (P = 0·00). A steady rise in MRSA infection rates began in 1995 in HIV-uninfected patients, peaking at 396·5 infections/100000 person-years in 2007. A more rapid rise in MRSA infection rates occurred in the HIV-infected group after 2000, peaking at 3592·8 infections/100000 in 2005. A declining trend in MRSA rates may have begun in 2008-2009. Comparing the ratio of MRSA to MSSA case counts, we observed that HIV-infected patients shouldered a greater burden of MRSA infection during most years of study follow-up compared to HIV-uninfected patients.