The effect of the proton pump inhibitor dexlansoprazole, an enantiomer of lansoprazole, on QT intervals was assessed after oral administration of a modified-release formulation of dexlansoprazole (dexlansoprazole MR). In this randomized, positive-comparator, placebo-controlled, 4-period crossover study, 40 healthy participants received single doses of dexlansoprazole MR 90 mg, dexlansoprazole MR 300 mg, moxifloxacin 400 mg, and placebo separated by 5-day washout intervals. Twenty-four-hour electrocardiograms were obtained at baseline and during each dosing period. The number and percentage of participants experiencing an increase in QT interval from baseline to maximum postdose value were evaluated during each dosing regimen, and pharmacokinetic profiles of dexlansoprazole and moxifloxacin were obtained. The mean maximum Fridericia-corrected QT (QT(cF)) intervals were similar for both doses of dexlansoprazole MR and placebo but were significantly greater with moxifloxacin (P < or = .001). With both doses of dexlansoprazole MR, the placebo-adjusted mean change from baseline in QT(cF) intervals was <5 ms, and the upper boundaries of the 95% 1-sided confidence intervals were <10 ms at all time points. Pharmacokinetic analysis indicated that QT intervals were measured at the time of maximum drug plasma concentration. Neither dexlansoprazole MR 90 mg nor 300 mg prolonged QT(cF) intervals in healthy participants. Both doses were well tolerated.