Background It is important to obtain greater insight into health-related quality of life (HRQL) of injury patients in order to document people's pathways to recovery and to quantify the impact of injury on population health over time. We performed a systematic review of studies measuring HRQL in general injury populations with a generic health state measure to summarize existing knowledge. Methods Injury studies (1995-2009) were identified with main inclusion criteria being the use of a generic health status measure and not being restricted to one specific type of injury. Articles were collated by study design, HRQL instrument used, timing of assessment(s), predictive variables and ability to detect change over time. Results Forty one studies met inclusion criteria, using 24 different generic HRQL and functional status measures (most used were SF-36, FIM, GOS, EQ-5D). The majority of the studies used a longitudinal design, but with different lengths and timings of follow-up (mostly 6, 12, and 24 months). Different generic health measures were able to discriminate between the health status of subgroups and picked up changes in health status between discharge and 12 month follow-up. Most studies reported high prevalences of health problems within the first year after injury. The twelve studies that reported HRQL utility scores showed considerable but incomplete recovery in the first year after discharge. Conclusion This systematic review demonstrates large variation in use of HRQL instruments, study populations, and assessment time points used in studies measuring HRQL of general injury populations. This variability impedes comparison of HRQL summary scores between studies and prevented formal meta-analyses aiming to quantify and improve precision of the impact of injury on population health over time.