Orange-fleshed sweet potato (OFSP) is currently promoted in parts of sub-Saharan Africa as a biofortified staple food with large potential to provide considerable amounts of provitamin A carotenoids. However, the bioaccessibility of provitamin A carotenoids from OFSP has not been widely investigated, especially not as an effect of different preparation methods. In this study, we used an in vitro digestion model to assess the bioaccessibility of beta-carotene from differently heat-processed OFSP. The fraction of carotenoids transferred from the food matrix to a micellar phase obtained after microfiltration and to a supernatant obtained after low-speed centrifugation was investigated. The percentage of accessible all-trans-beta-carotene in the micellar phase varied between 0.5 and 1.1% in the heat-processed OFSP without fat and between 11 and 22% with the addition of 2.5% (w/w) cooking oil. In comparison with the micellar phase, the percentage of accessible all-trans-beta-carotene in the supernatant phase was significantly higher (P < 0.001), between 24 and 41% without fat and between 28 and 46% with fat. These results support the importance of fat for an improved micellarization of beta-carotene. Overall, the high in vitro bioaccessibility of beta-carotene from heat-processed OFSP indicates that sweet potato might be a promising dietary approach to combat vitamin A deficiency.