Lopinavir, an HIV protease inhibitor, is coformulated with ritonavir to enhance the bioavailability and pharmacokinetics of lopinavir. The original solid oral formulation of lopinavir/ritonavir, a soft-gelatin capsule (SGC), requires refrigerated storage, is taken as 6 capsules daily at the recommended adult dose, and is administered with food to maximize the bioavailability of lopinavir. Melt extrusion technology was used to produce a tablet formulation reducing the number of dosage units administered per day and simplifying storage requirements. Three studies assessed the bioavailability of tablet doses of lopinavir/ritonavir at 800/200 mg or 400/100 mg under different meal conditions compared with equal doses of the SGC after a moderate-fat meal. The tablet was bioequivalent to the SGC after a moderate-fat meal with respect to lopinavir and ritonavir areas under the concentration-time curve. Compared with the SGC formulation, the tablet formulation resulted in more consistent lopinavir and ritonavir exposures within and across studies and across meal conditions. The diminished food effect and decreased variability of the tablet are likely to result in more consistent lopinavir and ritonavir exposures, minimizing the likelihood of extreme high or low values compared with the SGC.