Two experiments were used to evaluate the potential interaction of fat source and vitamin E (VE) in heavy slaughter weight pigs. In Experiment 1, a total of 64 individually-fed pigs (28.41 ± 0.83 kg) were randomly assigned to 8 dietary treatments in a 4×2 factorial arrangement. Fat treatments included cornstarch (CS), tallow (TW), corn-oil (CO), and coconut-oil (CN). VE treatments were dietary α-tocopheryl acetate (ATA) at 11 and 200 ppm. In Experiment 2, a total of 72 individually fed pigs (28.55 ± 1.16 kg) were randomly assigned to 12 dietary treatments in a 2 × 6 factorial arrangement. Fat treatments were TW and CO. VE treatments included four levels of ATA (11, 40, 100, and 200 ppm) and two levels of mixed tocopherols (primarily γ-tocopherol; 40 and 100 ppm). VE deposition, growth performance, and meat quality were measured in both experiments. In both experiments, interaction between fat sources and VE were detected (P < 0.01) on plasma VE concentration, which increased (P < 0.01) with time and with increasing dietary VE, but increased faster (P < 0.05) in pigs fed with CN and TW compared to pigs fed CS and CO. Compared to CO, more saturated dietary fat sources (CN and TW) led to firmer belly (P < 0.01), which had more (P < 0.01) SFA and MUFA while less (P < 0.05) Feed/Gain in Phase 4 and Phase 5. In Experiment 2, increasing dietary ATA increased overall ADG (linear, P = 0.02), with an interaction (P < 0.05) with fat sources on cumulative ADG during Phase 1-4, wherein pigs fed CO, but not TW, had increased ADG with increasing dietary ATA. Increasing dietary ATA increased (quadratic, P < 0.05) liver SOD activity, and decreased (quadratic, P < 0.05) liver MDA content. The oxidative stability of loin was improved (P < 0.01) when dietary ATA increased over 40 ppm. In summary, both dietary fat source and VE supplementation affected the response measures.