The study aimed to assess the effects of vitamin E (VE) supplementation and fat source on fatty acid (FA) composition, VE concentrations, and antioxidant capacity in plasma and tissues of pigs fed to a heavy slaughter weight (150 kg). A total of 64 pigs (32 barrows, 32 gilts; 28.41 ± 0.83 kg) were blocked by sex and weight, and randomly assigned to one of eight dietary treatments (n = 8 per treatment) in a 4 × 2 factorial arrangement. Fat sources included corn starch (CS), 5% tallow (TW), 5% distiller's corn oil (DCO), and 5% coconut oil (CN); VE supplementation levels were 11 and 200 ppm. Five-phase diets were formulated to meet requirement estimates of NRC (2012) and fed to pigs for each period of 25 kg from 25 to 150 kg. Increasing VE supplementation level increased C16:1 (P < 0.05) content but decreased C20:0 (P < 0.05) content in backfat and belly fat, while in liver, it increased C17:0 (P < 0.05) but decreased C18:0 (P < 0.05). Compared to the pigs fed the CS diet, the pigs fed the CN diet had greater (P < 0.05) content of total saturated FA, the pigs fed the DCO diet had greater (P < 0.05) content of total polyunsaturated FA content and iodine value, and the pigs fed the TW diet had greater (P < 0.05) content of total monounsaturated FA in backfat, belly fat, and liver. Plasma VE concentrations increased linearly (P < 0.05) with increasing length of feeding but faster (P < 0.05) in the pigs fed the CN and TW diets compared with the CS and DCO diets within the 200 ppm VE level; the pigs fed the DCO diet had the highest plasma VE concentrations (P < 0.05) from Phase 2 to Phase 5 within the 11 ppm VE level. The VE concentrations in liver and loin muscle (P < 0.05) increased with increasing dietary VE level from 11 to 200 ppm, but it was not affected by dietary fat source. There was no effect of VE supplementation and fat source on antioxidant capacity in plasma and liver except that pigs fed the DCO diet had greater liver SOD activity (P < 0.05) than the pigs fed the CN diet. In conclusion, dietary VE supplementation did not affect FA profile in backfat, belly fat, and liver consistently, while dietary FA composition with different fat sources affected much of the FA profile in backfat, belly fat, and liver. The higher level of VE supplementation increased liver and muscle VE concentrations and dietary fat sources affected plasma VE concentrations differently (P < 0.05), wherein the TW and CN diets increased the VE absorption greater than the DCO diet.