OBJECTIVE: The purpose of the present study was to examine the experimental and epidemiologic evidence linking benzodiazepine use to driving impairment. DATA SOURCES: We searched MEDLINE, PsycINFO, the Cochrane Collaboration, and EMBASE using the key terms ("benzodiazepines" OR "exp benzodiazepines") AND ("automobile driving" OR "accidents, traffic" OR "driving" OR "driver$") and limited the results to English citations from 1966 to August 5, 2005, with auto-updates for MEDLINE and PsycINFO to November 30, 2007. STUDY SELECTION AND DATA EXTRACTION: Experimental studies using driving simulators and on-road tests were sought, as were epidemiologic studies of a case-control or cohort design. Data were extracted by blinded raters and pooled using random-effects models. We excluded studies without control groups or without measures of driving or collisions. Studies with driving measures that could not be combined were also excluded. DATA SYNTHESIS: Of 405 potential articles, 11 epidemiologic and 16 experimental studies were included in the meta-analysis. Associations between motor vehicle collisions (MVCs) and benzodiazepine use were found among 6 case-control studies (OR = 1.61, 95% CI = 1.21 to 2.13, p <.001), and 3 cohort studies (OR = 1.60, 95% CI = 1.29 to 1.97, p <.0001). Only 10 of 97 experimental driving variables could be pooled for analysis. While no consistent findings were observed in studies using driving simulators, increased deviation of lateral position was found on on-road driving tests (standardized mean difference = 0.80, 95% CI = 0.35 to 1.25, p = .0004). CONCLUSION: Benzodiazepine users were found to be at a significantly increased risk of MVCs compared to nonusers, and these differences may be accounted for by a difficulty in maintaining road position.