The release of arsenic (As) from a contaminated food matrix during gastrointestinal digestion, i.e., its bioaccessibility, is an important estimator of its bioavailability, and therefore also its health risk. In addition, As toxicity is primarily determined by its speciation and it is not clear how different As species behave during digestion in the upper digestive tract. Here, we evaluated to what extent digestive parameters like gastric pH and bile concentration, but also food matrix constituents affect the bioaccessibility of 8 As species (As(III), As(V), MMA(V), DMA(V), MMA(III), DMA(III), MMMTA(V), DMMTA(V)). Bioaccessibility of all As standards ranged between 85% and 90% under pH 1.8. Bioaccessibility of methylated and thiolated arsenicals was decreased from 85% to 50% with increasing gastric pH to 4, yet an increasing bile salts concentration up to 30 g/L lowered the bioaccessibility of inorganic species from 83% to 70% due to interaction with Fe present in bile salts. With respect to food matrices, we noted that the fiber content did not affect As bioaccessibility, yet the presence of fat resulted in an increased bioaccessibility of both inorganic and organic arsenicals in the presence of bile salts. With respect to inorganic arsenic, the intestinal presence of trivalent Fe appeared to be the predominant factor for bioaccessibility of iAs. These data demonstrate that species dependent bioaccessibility must be considered upon ingestion and gastrointestinal digestion.