Rationale The diagnostic concordance between transbronchial lung cryobiopsy (TBLC) -- versus surgical lung biopsy (SLB) as the current gold standard -- in interstitial lung disease (ILD) cases requiring histology remains controversial. Objectives To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. Methods A two-center prospective study included ILD patients with a non-definite usual interstitial pneumonia (UIP) pattern (on HRCT scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open-reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (TVC). Kappa-concordance coefficients and % agreement were computed for: TBLC-vs-SLB; MDA2-vs-TBLC; MDA2-vs-SLB, and blinded pathology versus routine pathology. Measurements and Main Results Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range: 5-8). SLB biopsy sizes averaged 46.1 ± 13.8 mm. Concordance coefficients and % agreement were: TBLC-vs-SLB: K=0.22(95%CI: 0.01-0.44), %agreement=38%(95%CI: 18-62); MDA2-vs-TBLC: K=0.31(95%CI: 0.06-0.56), %agreement=48%(95%CI: 26-70); MDA2-vs-SLB: K=0.51(95%CI: 0.27-0.75), %agreement=62%(95%CI: 38-82)); Two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11/21 (52%) of cases. Conclusion Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA.