OBJECTIVES:  When there are no direct head-to-head trials versus an appropriate comparator, indirect comparisons are commonly performed to support a clinical claim and relative pricing.  In Australia, Public Summary Documents (PSDs), reporting on the Pharmaceutical Benefits Advisory Committee’s (PBAC) decision-making process relating to government reimbursement of medicines, have been published since July 2005. A review of PSDs specific to drugs where the primary claim was based on indirect evidence was undertaken to assess the success of the approach and identify the PBAC’s main concerns relating to the methodology. METHODS:  All PSDs published between July 2005 and November 2012 where the primary evidence was based on an indirect comparison, either as simple or a mixed treatment comparison, were reviewed.  Data relating to comparator, clinical claim, economic analysis, and PBAC concerns were extracted and analysed. RESULTS:  PSDs relating to 105 products using an indirect comparison as the primary analysis were reviewed.  A total of 70 (67%) submissions were recommended; the remaining submissions were rejected (32, 30%) or deferred (3, 3%).  An indirect comparison was used to support a non-inferiority claim in 84 (80%) submissions and superiority claim in 21 (20%) submissions.   Of those claiming non-inferiority, 60 (71%) submissions were recommended by the PBAC.  Of those claiming superiority, the PBAC accepted the clinical claim for 10 (48%) submissions; 6 (29%) received a price premium.  The PBAC expressed concerns relating to the indirect comparisons in 56 (53%) PSDs.  The key issues related to the exchangeability of the trials as a consequence of different patient populations (25%), quality of trials (24%), and dosing (18%). CONCLUSIONS:  Clinical comparisons based on indirect evidence are associated with increased uncertainty related to the exchangeability of the trials.  The PBAC usually accepts evidence to support a claim of non–inferiority, but rarely the same in regards to superiority.