OBJECTIVES: In Australia, the Pharmaceutical Benefits Advisory Committee (PBAC) makes recommendations to the Minister for Health on the reimbursement of pharmaceuticals. The sponsor’s submission is accepted by the PBAC if the drug is determined to be clinically effective and also cost-effective. New PBAC Guidelines on how to prepare a submission (version 4) were introduced in 2008. These new Guidelines sought to reduce the uncertainty for the PBAC in accepting the many inferences made in major submissions. We assessed whether the New Guidelines have indeed reduced the PBAC’s uncertainty in their decision making.  METHODS: Since June 2003 all PBAC recommendations have been made public on the Department of Health & Ageing website. Public Summary Documents (PSD) are available for PBAC considerations relating to the PBS listing of medicines since July 2005 meeting.  We reviewed all the PSDs reported during the period of July 2005 to July 2009. For each PSD, we estimated the average number of times that the words “uncertain/uncertainties/uncertainty” appear per PSD page. We compared the results for the period before and after the introduction of version 4 of the PBAC Guidelines. RESULTS: The average number of times that the words “uncertain/uncertainties/uncertainty” appeared per PSD page was significantly higher for the period after the introduction of version 4 of the PBAC Guidelines compared to the period before (0.51 vs. 0.66, P<0.00001). CONCLUSIONS: The introduction of version 4 of the PBAC Guidelines in 2008 has led to an increase in the complexity and, thus, uncertainty faced by PBAC during their deliberations around reimbursement of pharmaceuticals in Australia. There was a significant 30% increase in the number of times that the word “uncertain/uncertainties/uncertainty” was found per PSD page compared with the period prior to the introduction of the version 4 of the Guidelines (2003-2008).