Prolactinomas account for ∼40% of all pituitary adenomas and are important causes of infertility and gonadal dysfunction. In general, most prolactinomas are treated medically with dopaminergic agonists, while surgery is reserved for patients intolerant or nonresponsive to these medications. The aim of this study was to carry out a comparative analysis of the cost-effectiveness of medical therapy with bromocriptine and surgical therapy with trans-sphenoidal surgery. A Markov model was developed based on retrospective data from 126 patients with prolactinoma treated in our hospital between October 2008 and May 2009, and from data published previously. For patients with microadenoma, the cost of medical treatment was estimated to be ¥20,555, while the cost of surgery was calculated to be ¥22,527. For patients with macroadenoma, the cost of therapy with bromocriptine was ¥31,461 in males and ¥27,178 in females, while the cost of surgery was ¥42,357 in males and ¥44,094 in females. Sensitivity analyses (carried our using variations in patient age, bromocriptine therapeutic dose, bromocriptine maintenance dose, and the success rate of bromocriptine withdrawal) indicated that our model showed good stability, although our results were most heavily influenced by variations in the bromocriptine maintenance dose. It is concluded that, from an economic viewpoint, medical therapy with bromocriptine should be the first-line treatment option for patients with prolactinoma, irrespective of whether this is a microadenoma or macroadenoma.