In health technology assessment (HTA) agencies where cost-effectiveness plays a role in decision-making, an incremental cost-effectiveness ratio (ICER) threshold is often used to inform reimbursement decisions. The acceptance of submissions with ICERs higher than the threshold was assessed across different agencies and across indications, in order to inform future reimbursement submissions.All HTA appraisals from May 2000 to May 2014 from National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (PBAC), and Canadian Agency for Drugs and Technologies in Health (CADTH) were assessed. Multiple technology appraisals, resubmissions, vaccination programs, and requests for advice were excluded. Submissions not reporting an ICER, or for which an ICER could not be determined were also excluded. The remaining appraisals were reviewed, and the submitted ICER, recommendation, and reasoning behind the recommendation were extracted.NICE recommended the highest proportion of submissions with ICERs higher than the threshold (34% accepted without restrictions; 20% with restrictions), followed by PBAC (16% accepted without restrictions; 4% with restrictions), SMC (11% accepted without restrictions; 14% accepted with restrictions), and CADTH (0% accepted without restrictions; 26% with restrictions). Overall, the majority of higher-than-threshold ICER submissions were classified into the "malignant disease and immunosuppression" therapeutic category; however, there was no notable variation in acceptance rates by disease area. Reasons for accepting submissions reporting ICERs above the threshold included high clinical benefit over the standard of care, and addressing an unmet therapeutic need.Acceptance of submissions with higher-than-threshold ICERs varied by HTA agency and was not significantly influenced by disease category. Such submissions must be accompanied by robust, concrete, and transparent evidence in order to achieve patient access.