Objective: This pooled claims database study evaluated the risk of recurrent Venous Thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by high-risk subgroups. Methods: Patients diagnosed with VTE in the setting of active cancer who initiated apixaban, LMWH, or warfarin were identified using four US commercial claims databases from 01SEP2014 to the end of the study period (MarketScan: 01MAR2014-30JUNE2017; Optum and Humana: 01MAR2014-31DEC2017; PharMetrics: 01MAR2014-31MAR2018). Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate the risk of recurrent VTE and MB for each subgroup stratification: VTE risk level based on cancer types, metastatic diagnosis, cancer treatment, chemotherapy, gastrointestinal cancer, and index VTE event type (PE vs. DVT). Statistical significance (p < .10) of the interaction between treatment effects and subgroups was evaluated. Results: Eligible subjects included 3393 apixaban, 6108 LMWH, and 4585 warfarin patients. After IPTW, all patient characteristics were balanced. Analyses stratified by the VTE risk level, metastatic diagnosis, cancer treatment, chemotherapy, gastrointestinal cancer and index VTE event type showed generally consistent results according to the respective subgroup (most of the p values for interaction >0.10). Two significant interactions were observed between apixaban vs. LMWH and VTE risk level (interaction p ¼ .051) and metastatic diagnosis (interaction p < .001) for recurrent VTE; one significant interactions were observed between apixaban vs. LMWH and cancer treatment for MB (interaction p ¼ .074). Additionally, for warfarin vs. LMWH, two significant interactions were observed between treatment and VTE risk level (interaction p ¼ .005) and metastatic diagnosis (interaction p ¼ .002) for recurrent VTE. Conclusions: Across these high-risk subgroups of VTE cancer patients, treatment outcomes associated with apixaban were generally positive compared to LMWH and warfarin.