OBJECTIVES: To evaluate the implementation of National Institute for Health and Clinical Excellence (NICE) guidance across four hospitals in the NHS South of England region, and its impact on patient safety using the following outcome measures:  The percentage of patients for whom a risk assessment was documented; the percentage of patients who received venous thromboembolism (VTE) prophylaxis amongst those who were not risk assessed and the percentage of patients who received VTE prophylaxis amongst those with a contraindication to VTE prophylaxis. METHODS: A mixed method approach, which included a retrospective patient record review of VTE risk assessment documentation and prescribing of prophylaxis in patients without a risk assessment or a documented contraindication to VTE prophylaxis prior to and following the implementation of NICE guidance.  Qualitative methods in the form of semi-structured interviews were used to evaluate the implementation strategies employed by the four hospitals. RESULTS: The percentage of patients for whom a VTE risk assessment was documented increased from 51.5% (210/408) in 2009 to 79.2% (323/408) in 2010; difference 27.7% (95% CI: 21.4% to 33.9%; p<0.001). There was little evidence of change in the percentage who were prescribed prophylaxis amongst patients without a risk assessment (71.7% (142/198) in 2009 and 68.2% (58/85) in 2010; difference -3.5%% (95% CI: -15.2% to 8.2%; p =0.56) nor the percentage who were prescribed low molecular weight heparin amongst patients with a contraindication (14% (4/28) in 2009 and 15% (6/41) in 2010; RD = 0.3% (95% CI: -16.5% to 17.2%; p =0.97). CONCLUSIONS: The documentation of risk assessment clearly improved following the implementation of NICE guidance but this did not lead to improved patient safety in terms of increasing appropriate or decreasing inappropriate prescribing of prophylaxis.