Background: Previous studies revealed that surgical lung biopsy in usual interstitial pneumonia (UIP) patients is accompanied with higher morbidity and mortality. The aim of this retrospective analysis was to assess morbidity and mortality of patients with suspected UIP undergoing surgical lung biopsy. Methods: We conducted a retrospective study of 45 patients with suspected UIP pattern undergoing surgical biopsy for diffuse pulmonary infiltrates in our department. Data concerning medical history, histology, and survival status were extracted from the medical database of the University Medical Center Freiburg. Results: UIP was diagnosed by experienced pneumo-pathologists according to the criteria of American Thoracic Society/European Respiratory Society (ATS/ERS) consensus classification. Due to adhesions the surgeon decided in two patients to perform wedge resection via open surgery. In 43 patients lung biopsy was performed via Video-assisted thoracoscopy (VATS). No intraoperative complications were observed. Postoperative complications consisted of bradyarrhythmia (n = 1), gastrointestinal bleeding (n = 1), bacterial pneumonia (n = 1), candida pneumonia (n = 1) and acute exacerbation (n = 1). There was no 30-day mortality, but one patient was lost in follow-up and therefore censored. The intraoperative placed thoracic drain was removed at the first postoperative day in most cases (mean day of removal 1.9, ±2.6). The mean length of hospital stay was 8.1 days (±6.8). Conclusions: We conclude that surgical biopsy can be safely performed in patients with suspected UIP.