Introduction: Best practice guidelines recommend that at least two sets of blood cultures be sent when blood cultures are required. However, high rates of solitary blood cultures are still common in the emergency department. The aim of this study was to evaluate the efficacy of different quality improvement initiatives aimed at reducing the rate of solitary blood cultures being sent to the lab on patients ultimately discharged from our emergency department. Methods: This was a multi-centre, multi-phase, prospective study evaluating a comprehensive education-based intervention and a second intervention that combined a computerized forcing function along with a brief education-based intervention. The results were analyzed using segmented regression analysis, as well as statistical process control charts. Results: The baseline rate of solitary sets of blood cultures was 41.1%. The education intervention reduced this rate to 30.3%. The introduction of a forcing function with a brief educational intervention further reduced the rate to 11.6%. This represents an absolute reduction of 29.5% from baseline (relative reduction of 71.8%). According to segmental regression analyses, the education intervention alone did not produce a statistically significant change when factoring possible background time-related trends (P=0.071). However, the forcing function produced a statistically significant improvement (P < 0.0005), which was maintained for 6 months. Conclusion: The combination of a brief education-based intervention and a computerized forcing function was more effective than education alone in reducing solitary blood culture collection in our emergency department in this time series study. Forcing functions can be a powerful tool in modifying behaviours and processes in the clinical setting.