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OBJECTIVE: Lung cancer screening with annual Low-Dose CT (LDCT) reduces lung cancer death by 20-26%. However, potential harms of screening include false positive results, procedures from false positives, procedural complications and failure to adhere to follow-up recommendations. In diverse, underserved populations, it is unknown if benefits of early lung cancer detection outweigh harms. METHODS: We conducted a prospective observational study of lung cancer screening participants in an urban, safety-net institution from September 2014 to June 2020. We measured benefits of screening in terms of cancer diagnosis, stage and treatment. We measured harms of screening by calculating false positive rate, procedures as a result of false positive screens, procedural complications and failure to follow-up with recommended care. Of patients with 3-year follow up, we measured these same outcomes in addition to compliance with annual screening. RESULTS: Of 1509 participants, 55.6% were African American, 35.2% White, 8.1% Hispanic and 0.5% Asian. Screening resulted in cancer detection and treatment in 2.8%. False positive and procedure as a result of a false positive occurred in 9.2% and 0.8% of participants, respectively with no major complications from diagnostic procedures or treatment. Adherence to annual screening was low, 18.7%, 3.7% and 0.4% at 1, 2 and 3 years after baseline screening respectively. CONCLUSIONS: Multidisciplinary lung cancer screening in a safety-net institution can successfully detect and treat lung cancer with few harms of false positive screens, procedure after false positive screens and major complications. However, adherence to annual screening is poor.