Objectives The aim of this study was to evaluate the cost effectiveness of mirabegron relative to two antimuscarinics, oxybutynin extended release (ER) and tolterodine ER, in patients with overactive bladder (OAB) from the perspective of a third-party payer in Colombia. Methods A Markov model simulated the therapeutic management, disease course, and complications in hypothetical cohorts of OAB patients over a 5-year period. The model predicted costs and three outcomes: quality-adjusted life-years (QALYs), micturition state improvement (MSI), and incontinence state improvement (ISI). In each 1-month cycle, patients could transition between different health states reflecting symptom severity. Transition probabilities were estimated from a published mirabegron trial and mixed treatment comparison. Other inputs such as treatment discontinuation based on treatment-specific rates of persistence, resource use and costs, anticholinergic burden, comorbidity treatment, and drug acquisition were obtained from Società Italiana Scienze Mediche, Instituto de Seguros Sociales Tariff Manual, published literature, and expert opinion. Deterministic and probabilistic sensitivity analyses were conducted. Costs are presented in 2017 Colombia Pesos (COP). Results Mirabegron was cost effective for all outcome measures at a willingness-to-pay threshold of 124,919,725 COP, which is three times the per capita gross domestic product (GDP). Using QALYs as the measure of effect, mirabegron had an incremental cost-effectiveness ratio (ICER) of 85,802,036 COP/QALY (26,365 USD/QALY) and 66,360,134 COP/ QALY (20,384 USD/QALY) versus oxybutynin and tolterodine, respectively. Probabilistic sensitivity analyses showed that mirabegron was cost effective in 99.5% and 100% of simulations compared with oxybutynin and tolterodine, respectively. Using MSI and ISI as the measure of effects yielded ICERs below one GDP. Conclusions Mirabegron is a cost effective alternative to oxybutynin and tolterodine from the perspective of a third-party payer in Colombia.