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There are no data that compare the clinical presentation and results of surgical lung biopsy (SLB) for diffuse lung disease (DLD) in lung transplant patients, in contrast to individuals with other type of solid organ grafts. Our objective was to compare the clinical picture, radiologic pattern, pathology results, and outcomes of SLB for DLD in these two subsets of patients.We retrospectively reviewed the clinical records of transplant patients undergoing SLB for DLD at our institution between 2004 and 2011. Patients with lung transplants and those with other transplants were compared.During the study period, 1,232 solid organ transplants were done at our institution. Of these, 49 patients (4%) had DLD that needed SLB for diagnosis, and 24 of these patients had a lung transplant. Dyspnea and a radiologic reticular pattern were more frequent in lung transplant patients, 21 of 24 vs 11 of 25 (p = 0.001) and 14 of 24 vs 7 of 25 (p = 0.03), respectively. Although postoperative complications and in-hospital deaths were more common in lung transplant patients, the differences were not statistically significant. Having the SLB performed for diagnosis, as opposed to being conducted for DLD that did not improve on medical treatment, had a protective effect on multivariate analysis (hazard ratio, 0.39; 95% confidence interval, 0.16 to 0.96; p = 0.042). A prior lung transplant was the only independent predictor of survival (hazard ratio, 4.62; 95% confidence interval, 1.53 to 13.92, p = 0.006).It is relatively uncommon for a solid organ transplant patient with DLD to require a SLB. Clinical and radiologic presentation differ in patients with lung transplants compared with other transplants. Postoperative outcomes are not significantly different between the groups. SLB performed early in the course of the disease might be beneficial. Having a lung transplant is a significant negative predictor of survival.