This study aimed to assess the comparative bioavailability between ibuprofen acid orodispersible tablets (Test product) and ibuprofen acid oral tablets (Reference product). This was a randomized, single-dose, 3-way crossover, open-label, pharmacokinetic study in 36 healthy male and female volunteers. Blood samples were taken periodically over a 12-h period after dosing to derive total plasma ibuprofen and S(+)/R(-) ibuprofen enantiomer pharmacokinetic parameters; safety profile and tolerability were evaluated throughout the study. After a single-dose administration of ibuprofen acid oral tablets (2 × 200 mg), the total ibuprofen Cmax and AUC0-t (geometric least square [LS] mean) for the Test product was 29.4 μg/mL and 100.6 h/μg/mL, respectively, and for the Reference product it was 30.6 μg/mL and 98.7 h/μg/mL. The geometric LS mean Test/Reference ratio 90% CI for both total ibuprofen Cmax (90.71-101.77) and AUC0-t (98.72-105.23) was contained entirely within the predefined 80.00%-125.00% lower and upper limits; in addition, no statistically significant difference was found in Tmax (P = 0.1819) after fasted administration of the Test and Reference products. There were 4 mild treatment emergent adverse events, considered unrelated to the study drug, reported by 2 volunteers during the study; no serious adverse events, no suspected unexpected serious adverse events. and no clinically significant changes in laboratory safety, vital signs, or 12-lead ECG measurements were reported. The enantiomer-specific analysis mirrored that of total ibuprofen, with the Cmax and AUC0-t LS mean Test/Reference ratio 90% CI for both ibuprofen S(+) and R(-) enantiomers contained entirely within the predetermined 80%-125.00% limits. This study found that ibuprofen acid 200 mg orodispersible tablets and ibuprofen acid 200 mg tablets met the regulatory criteria for bioequivalence for AUC0-t and Cmax. Post hoc analysis of ibuprofen both S(+) and R(-) enantiomers mirrored the findings for total ibuprofen. All investigational products were found to be well tolerated. Clinicaltrials.gov identifier: NCT03180879.