Among 435 patients without native valve endocarditis who were followed up to 69 months after primary mitral valve replacement, 25 developed documented periprosthetic leakage. In 10 patients this was associated with prosthetic valve infection. No evidence of prosthetic infection was found in the remaining 15 patients with documented leakages, and they form the basis of the study. Multivariate Cox regression analysis indicated that leakage in the absence of infection was strongly associated with the use of small monofilament suture (2-0 or 3-0 versus 1-0) in a continuous suture technique (92.0% actuarially leak free by 43 months versus 99.0% for continuous 1-0 monofilament sutures or pledgeted mattress sutures; p = 0.01) and with annular calcification (p = 0.01). We did not find (p greater than 0.2) the functional type of mitral valve lesion or its pathology, or the type and size of prosthesis used, to be incremental risk factors.