BACKGROUND Skin and soft tissue infections caused by nontuberculous mycobacteria (NMT) are reported to be associated with injections, liposuction, plastic surgery, and acupuncture. Herein, we describe an outbreak of soft tissue infection due to NMT following mesotherapy, a cosmetic procedure involving injection of poorly defined mixtures alleged to reduce local adiposity. METHODS Patients with skin lesions and a history of mesotherapy treatment, who visited the dermatology department of the public hospital in Barinas, Venezuela, from November 2004 to February 2005 were interviewed. Clinical and environmental samples were taken for mycobacteria isolation. RESULTS The interviews revealed that 68 patients who had been treated for cosmetic purposes at the same clinic by the same therapist had received injections with the same product and were infected with NMT. Clinical specimens from 5 patients grew Mycobacterium abscessus. No mesotherapy solution was available for analysis but M. abscessus was isolated from an environmental sample in the clinic. PCR-based strain typing techniques (ERIC-PCR, BOXA1R and RAPD) showed that the patient's isolates were undistinguishable from each other but different from the environmental isolate. CONCLUSIONS This outbreak was likely caused by a contaminated injectable mesotherapy product and not by mycobacteria from the clinic environment. We emphasize the importance of better microbiological control of these products. To our knowledge, this outbreak, which affected at least 68 patients, appears to be the largest ever associated with mesotherapy and described in the literature.