Bronchoscopic biopsies have limited sensitivity for small, peripheral lung nodules. Electromagnetic navigation guided bronchoscopy (ENB) with fluoroscopic digital tomosynthesis and a 1.1 mm cryoprobe for transbronchial lung cryobiopsy (TBLC) may improve diagnostic yield. We evaluated the diagnostic yield and safety of this approach. 42 patients (45 nodules) underwent sequential biopsies by transbronchial needle aspiration (TBNA), then forceps biopsy (FB), and finally TBLC. Demographic data, nodule characteristics, biopsy results, and procedural complications were recorded. Nodules were predominantly solid (n = 35, 78%), without a bronchus sign (n = 30, 67%), and 33% (n = 15) were <2 cm in all dimensions (mean axial: 25.7 ± 15.3 mm, coronal: 21.0 ± 10.1 mm, sagittal 25.5 ± 16.5 mm). TBNA was the most informative biopsy modality (31/45 diagnoses total, five unique, 69% modality diagnostic yield (MDY)) compared to FB (27/45, one unique, 60% MDY) or TBLC (27/45, six unique, 60% MDY). FB contributed four additional diagnoses, improving diagnostic yield to 80% (36/45). TBLC contributed six additional diagnoses for a final diagnostic yield of 93% (42/45). No bleeding that required intervention or pneumothoraxes occurred. In unadjusted logistic regression models, solid nodules had increased odds of obtaining a diagnosis with TBNA (OR: 5.06; 95% CI: 1.14-22.49) and increased axial dimension nodule size had increased odds of obtaining a diagnosis with TBLC (OR: 1.10; 95% CI: 1.02-1.19). ENB guided TBLC of lung nodules appears safe and may increase the final diagnostic yield when combined with other modalities. Future studies identifying nodule characteristics and comparing biopsy tools may clarify the most efficacious approach to maximize yield and minimize risk.