Acidic dissociation constant (pKa) is an important physicochemical parameter in absorption, dissociation and elimination mechanisms of drugs in body. Various analytical methods are utilized for the determination of pKa values of pharmaceutical active ingredients, and potentiometry, spectrophotometry and HPLC are the most common methods. Cabergoline is dopaminergic ergoline derivative having a powerful and long-term prolactin reducing effect, which is used for the treatment of Parkinson disease. Tadalafil leads an increasing cGMP level in Corpus cavernous, during secretion of nitric oxide in sexual arousal. In the presented study, detection of pKa values for Cabergoline and Tadalafil by using potentiometry, spectrophotometry and HPLC was investigated. The pKa value for Cabergoline was respectively found to be 6.42, 6.05 and 6.20 by spectrophotometry, potentiometry and HPLC. Spectrophotometric pKa value was significantly different (p>0.05) from others, and potentiometry and spectrophotometry were appropriate for pKa value determination of Cabergoline. The pKa values for Tadalafil by potentiometry and spectrophotometry were found to be 3.52 and 3.44, respectively. But, in HPLC, no differentiation was observed in retention times of Tadalafil by increasing pH value of mobile phase. Developed methods for determination of pKa values for Cabergoline and Tadalafil demonstrated high repeatability values (RSD<%1). In this study, experimental pKa values for Cabergoline and Tadalafil from developed methods were compared with the values calculated by the common softwares and high-level divergences were observed.