The oral bioavailability of ibrutinib is low and variable, mainly due to extensive first‐pass metabolism by cytochrome P450 (CYP) 3A4. The unpredictable exposure can compromise its safe and effective dosing. We examined the impact of itraconazole on ibrutinib pharmacokinetics. In a randomized crossover study, 11 healthy subjects were administered itraconazole 200 mg or placebo twice on day 1, and once on days 2–4. On day 3, 1 hour after itraconazole (placebo) and breakfast, ibrutinib (140 mg during placebo; 15 mg during itraconazole) was administered. Itraconazole increased the dose‐adjusted geometric mean area under the concentration‐time curve from zero to infinity (AUC0–∞) of ibrutinib 10.0‐fold (90% confidence interval (CI) 7.2–13.9; P < 0.001) and peak plasma concentration (Cmax) 8.8‐fold (90% CI 6.3–12.1; P < 0.001). During itraconazole, the intersubject variation for the AUC0–∞ (55%) and Cmax (53%) was around half of that during placebo (104%; 99%). In conclusion, itraconazole markedly increases ibrutinib bioavailability and decreases its interindividual variability, offering a possibility to improved dosing accuracy and cost savings.