In this three-phase study we first compared the availability of fourteen Fe forms in a wheat-based ready-to-eat breakfast cereal using an in vitro digestion/human colonic adenocarcinoma (CaCo-2) cell model. We then investigated the effect of milk and/or coffee on those fortified cereals found in phase 1 to show promising increases in Fe availability. The Fe forms assessed in phase 1 were reduced (control), carbonyl, electrolytic, FePO4, FeSO4, FeCO3, Na2FeEDTA, Ferrochel® (Albion Laboratories, Clearfield, UT, USA; ferrous bis-glycinate), encapsulated ferrous fumarate, FeSO4, ferrous lactate and Biofer® (LipoTech, Britwell Salome, Oxfordshire; FeSO4), SQM® (Sea-Questra-Min Iron; Quali Tech, Chaska, MN, USA; polysaccharide-complexed FeSO4) and Sun Active® (Taiyo Kagaku, Yokkaichi, Japan). All these forms increased Fe uptake compared with the unfortified cereal. Relative to the control, the following increases in Fe availability were observed: electrolytic, 52 %; ferrous fumarate, 30–35 %; Sun Active, 78 %; Ferrochel, 125 %; Na2FeEDTA, 291 %. Recent human studies have shown similar data with regard to Ferrochel, FeSO4 and Na2FeEDTA, with the latter being more bioavailable. Our phase-2 studies indicated that the addition of milk to FeSO4-fortified cereal increased Fe availability, but this availability was markedly decreased by the addition of coffee to the digest. Conversely, a loss in availability from Na2FeEDTA was observed with the addition of milk; however, the addition of coffee did not markedly affect Fe availability from this form. In phase-3 studies we observed increased Fe availability upon the addition of milk to cereals containing Ferrochel, FeSO4, Sun Active, a mixture of reduced Fe and Na2FeEDTA or reduced Fe. For these forms we did not assess the behaviour after the addition of coffee. In conclusion, when considering possible fortificants for optimizing Fe bioavailability within a foodstuff, it is of paramount importance to consider the interaction between the fortified foodstuffs and other components of the meal (such as milk and coffee with a breakfast).