OBJECTIVES: Our objective was to compare the cost-effectiveness of the two most used valganciclovir-based cytomegalovirus (CMV) prophylaxis strategies, in intermediate risk renal transplant patients in Colombia. The two alternatives are “universal prophylaxis” strategy, which uses valganciclovir for the first 90 days post-transplantation, and “anticipated therapy”, which requires weekly viral load surveillance, warranting therapy only when positive. METHODS: We designed a TreeAge-based third party payer perspective (Colombian healthcare system) decision tree, considering only direct medical costs, in 2014 Colombian pesos (1 USD = 2000 COP) and a time horizon of one year. Target population was intermediate CMV risk patients (positive receptor). Transition probabilities were extracted from clinical studies, validated with a Delphi expert panel method; procedural costs were obtained from the official tariff manual (ISS 2001) with a 33% adjustment based on the health component of the Colombian Consumer Price Index for the year 2014. Medication costs were obtained from the official Ministry of Health information system (SISMED). RESULTS: Universal prophylaxis with valganciclovir was dominant, with lower costs and less probability of infection. The average cost of the first year in anticipated therapy would be US$ 15,481, whereas in the case of universal therapy the cost would be slightly lower US$ 14,984 (incremental cost of US$ 497). Results did not change significantly with deterministic and probabilistic sensitivity analyses. CONCLUSIONS: For Colombian renal transplant patients with an intermediate risk of CMV infections, universal prophylaxis strategy should be the best option.