The thumb carpometacarpal (CMC) joint is frequently affected by osteoarthritis (OA). The prevalence of thumb CMC OA greatly increases with age and has disproportional predominance in postmenopausal women. However, so far the etiology of thumb CMC OA remains unclear, and no conclusion has been achieved regarding the selection of the optimal surgical procedure. Joint contact mechanics can be an important aspect in understanding the mechanism of thumb CMC OA development. The contact pressure distribution on the articular surface directly affects the cartilage condition. This study quantitatively compared the in vivo thumb CMC joint contact mechanics between 4 males and 4 females using finite element modeling (FEM), and also evaluated the accuracy of a time-efficient surface-based contact modeling (SCM) procedure for possible clinical application. Although a sufficient statistical power cannot be achieved with the small number of subjects, the contact patterns were substantially different between male and female groups. Contact area, force and peak contact pressure showed a trend of increase in the older female subjects. Compared with FEM, the contact parameter values from SCM may be somewhat less accurate, but SCM produced contact distribution patterns similar to FEM. In addition, SCM was able to distinguish the different contact patterns between normal and osteoarthritic thumb CMC joints with much less data processing. Therefore, SCM has clear potential for future clinical diagnosis and the evaluation of treatment efficacy for thumb CMC OA.