Background: Results from the National Lung Screening Trial (NLST) in 2011 showed that low-dose CT screening in high-risk groups reduces lung cancer deaths. Major professional organizations, as well as the USPSTF, have endorsed low-dose CT screening in these select populations. However, major questions remain about whether widespread deployment of CT screening can achieve results similar to the NLST, especially in the community setting. Methods: A prospective cohort study was initiated in November 2010. High-risk participants (age at least 50 years old and history of cigarette smoking of at least 20 pack-years) underwent low-dose CT screening, performed and interpreted at El Camino Hospital in Mountain View, California. Diagnostic follow-up for positive scans were recommended per International Early Lung Cancer Action Program (I-ELCAP) guidelines. Participants were followed for events that occurred through December 31, 2013. Results: 157 participants underwent low-dose CT screening with mean follow-up of 2.2 years. Median age at entry was 64 (range 50-95). 59% of the participants are women and 94% are Caucasian. Over 80% also satisfied the more stringent NLST inclusion criteria for smoking history. The rate of positive initial screening tests was 35.7%. One positive screen (3.2%) required invasive diagnostic follow-up, which was uncomplicated. No interval lung cancer was detected. One incident case of small cell lung cancer resulted in death. The rate of timely adherence to diagnostic follow-up was only 43%. Late follow-up was often due to participant or primary care provider preference (68%), with participants lost to follow-up (18%) and lack of insurance (10%) also contributing. Conclusions: To our knowledge, this is the first community-based prospective study of low-dose CT lung cancer screening. Compared to the NLST, the higher rate of positive initial screening tests (36% vs 27%), higher overall false positive rate, and significantly decreased adherence (43% vs 95%) in this study highlight the difficulties of generalizing the NLST mortality benefits in the broad deployment of CT screening. Our results support current recommendations that CT screening be performed in a highly structured and integrated setting.