A new liquid capsule formulation of low-dose diclofenac-K in 12.5 mg and 25 mg dosages has been developed to provide the patient with an easier to swallow form than the current low-dose tablets. The new formulation is expected to have a faster rate of absorption and comparable overall bioavailability compared with the tablet formulations. To compare the systemic bioavailability of diclofenac from the new 25 mg liquid capsule vs. the currently registered diclofenac-K 2 × 12.5 mg tablets, and to evaluate the safety of the 25 mg liquid capsule. In this randomized, open-label, crossover, comparative bioavailability study, 42 healthy subjects (mean age 23.2 years) were given a single dose of diclofenac-K 25 mg liquid capsule or 2 × 12.5 mg tablets over 1-day treatment periods, separated by a washout period of 14 days. The total systemic exposure to diclofenac, as measured by the mean AUCs, was equivalent between treatments. However, the geometric mean Cmax for the 25 mg liquid capsule was almost double that of 2 × 12.5 mg tablets (1,058.2 vs. 564.5 ng/ml), while the median tmax was 5 minutes faster with the 25 mg liquid capsule and the geometric mean AUCtmax ref for the 25 mg liquid capsule (133.0 ng×h/ml) was much higher than for 2 × 12.5 mg tablets (91.6 ng×h/ml). The estimated AUCtmax ref ratio of 25 mg liquid capsule to 2 × 12.5 mg tablets was 143.1%, indicating much higher early exposure to diclofenac from the 25 mg liquid capsule. Both formulations were very well tolerated and only one adverse event was considered drug related (headache after taking the diclofenac-K 25 mg liquid capsule). Diclofenac-K 25 mg liquid capsule was equivalent to diclofenac-K 2 × 12.5 mg tablets in terms of overall systemic exposure to diclofenac. However, the rate of absorption of diclofenac was much faster from the liquid capsule than from the tablets, with a much greater early exposure to diclofenac. Both formulations were very well tolerated.