ABSTRACT: BACKGROUND:Mycetoma is a neglected tropical disease characterized by nodules, scars, abscesses, and fistulae that drain serous or purulent material containing the etiological agent. Mycetoma may be caused by true fungi (eumycetoma) or filamentous aerobic bacteria (actinomycetoma). Mycetoma is more frequent in the so-called mycetoma belt (latitude 15° south and 30° north around the Tropic of Cancer), especially in Sudan, Nigeria, Somalia, India, Mexico, and Venezuela. The introduction of new antibiotics with fewer side effects, broader susceptibility profiles, and different administration routes has made information on actinomycetoma treatment and outcomes necessary. The objective of this report was to provide an update on clinical, therapeutic, and outcome data for patients with actinomycetoma attending a reference center in northeast Mexico. METHODOLOGY/PRINCIPAL FINDINGS:This was a retrospective, cross-sectional, descriptive study of 31 patients (male to female ratio 3.4:1) diagnosed with actinomycetoma by direct grain examination, histopathology, culture, or serology from January 2009 to September 2018. Most lesions were caused by Nocardia brasiliensis (83.9%) followed by Actinomadura madurae (12.9%) and Actinomadura pelletieri (3.2%). About 50% of patients had bone involvement, and the right leg was the most commonly affected region in 38.7% of cases. Farmers/agriculture workers were most commonly affected, representing 41.9% of patients. The most commonly used treatment regimen was the Welsh regimen (35.5% of cases), a combination of trimethoprim/sulfamethoxazole (TMP/SMX) plus amikacin, which had a 90% cure rate, followed by TMP/SMX plus amoxicillin/clavulanic acid in 19.4% of cases with a cure rate of 100%. In our setting, 28 (90.3%) patients were completely cured and three (9.7%) were lost to follow-up. Four patients required multiple antibiotic regimens due to recurrences and adverse effects. CONCLUSIONS/SIGNIFICANCE:In our sample, actinomycetoma was predominantly caused by N. brasiliensis. Most cases responded well to therapy with a combination of TMP/SMX with amikacin or TMP/SMX and amoxicillin/clavulanic acid. Four patients required multiple antibiotics and intrahospital care.