we studied the pathogenesis of puffy hand syndrome of intravenous drug use we hypothesized that injections of high dose sublingual buprenorphine instead of the recommended sublingual administration could play an important role in lymphatic obstruction and destruction we set up a case control study in substitution centres recruiting intravenous drug addicts with and without puffy hands respectively the subjects were asked to answer anonymously a questionnaire of 40 items comprising social and demographic status history of illicit drugs use buprenorphine misuse and injection practices we included 33 cases and 33 controls mean age of 34 years they were past heroin users mainly methadone substituted in multivariate analysis sex women or 8 9 p 0 03 injections in the hands or 5 9 p 0 03 injections in the feet or 6 5 p 0 01 and the absence of tourniquet or 7 0 p 0 02 were significant risk factors for puffy hand syndrome in 69 7 of the cases and 59 4 of the controls respectively there was a high dose sublingual buprenorphine misuse although it appeared not to be a significant risk factor for puffy hand syndrome injection practices are likely to cause puffy hands syndrome but buprenorphine misuse should not be considered as a significant risk factor however intravenous drug users must still be warned of local and systemic complications of intravenous drug misuse.