Background: Cost avoidance occurs when, because of provision of a drug therapy [drug cost avoidance (DCA)] or a pathology test [pathology cost avoidance (PCA)] during trial participation, health care payers need not pay for standard treatments or testing. The aim of our study was to estimate the total DCA and PCA for Canadian patients enrolled in relevant phase III trials conducted by the NCIC Clinical Trials Group. Methods: Phase III trials that had completed accrual and resulted in DCA or PCA were identified. The PCA was calculated based on the number of patients screened and the test cost. The DCA was estimated based on patients randomized, the protocol dosing regimen, drug cost, median dose intensity, and median duration of therapy. Costs are presented in Canadian dollars. No adjustment was made for inflation. Results: From 1999 to 2011, 4 trials (1479 patients) resulted in PCA and 17 trials (3195 patients) resulted in DCA. The total PCA was estimated at $4,194,849, which included testing for KRAS ($141,058), microsatellite instability ($18,600), and 21-gene recurrence score ($4,035,191). The total DCA was estimated at $27,952,512, of which targeted therapy constituted 43% (five trials). The combined PCA and DCA was $32,147,361. Conclusions: Over the study period, trials conducted by the NCIC Clinical Trials Group resulted in total cost avoidance (PCA and DCA) of approximately $7518 per patient. Although not all trials lead to cost avoidance, such savings should be taken account when the financial impact of conducting clinical research is being considered.