OBJECTIVES: Open-label uncontrolled trials of ponatinib (PACE) and bosutinib (NCT00261846; published by Khoury 2012) in CP-CML suggest ponatinib is more efficacious than bosutinib in third-line patients. However, lack of head-to-head randomized trials comparing third-line treatments poses a challenge for clinical and reimbursement decisions. Future trials in third-line CP-CML are unlikely; therefore, to address this evidence gap, we indirectly compared efficacy in PACE versus the bosutinib trial using IPF to adjust for differences in baseline characteristics.  METHODS: We examined the subgroup of third-line CP-CML patients in the ponatinib and bosutinib trials, using patient-level data from PACE and the published bosutinib data. IPF was used to reweight the PACE patient-level data so that the reweighted baseline patient characteristics matched the aggregate bosutinib patient characteristics, including gender (male/female), race (white/nonwhite), median age (<56.0/ ≥56.0 years), median time since diagnosis (<6.7/≥6.7 years), ECOG performance status (0/≥1), and T315I mutation at study entry (yes/no). The model was fit using maximum likelihood. Efficacy in terms of major (MCyR) and complete (CCyR) cytogenetic response, and major molecular response (MMR) within 12 months are reported. Confidence intervals were simulated by bootstrap resampling of the PACE data. RESULTS: When reweighted to match bosutinib patient characteristics, the percent of ponatinib patients achieving MCyR (64.1% [95% CI: 55.3%-72.9%]), CCyR (52.3% [43.2%-61.5%]) and MMR (38.2% [29.3%-47.1%]) were consistent with unadjusted results (MCyR: 64.2%, CCyR:  53.8%, MMR: 43.4%) and exceeded efficacy observed with bosutinib in third-line CP-CML (MCyR: 31.7%, CCyR: 23.1%, MMR: 14.7%). Sensitivity analyses eliminating T315I status from the weighting yielded similar results.  CONCLUSIONS: Adjusted ponatinib efficacy outcomes in third-line CP-CML were similar to unadjusted, and efficacy was more than double that observed with bosutinib, irrespective of T315I mutation status. These results suggest that the higher efficacy observed in PACE (ponatinib) versus the bosutinib trial is not due to bias in patient selection.