Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (- )-epicatechin may reduce the risk of cardiovascular diseases. The interaction of ( - )-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (- )-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 3 ′- O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of ( - )-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 3′-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 3′-O-methyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this ( - )-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of ( - )-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting ( - )-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile.