Colonoscopy is currently regarded as the gold standard and preferred method of screening for colorectal cancer (CRC). However, the benefit of colonoscopy screening may be blunted by low participation rate in population-based screening program. Harmful effects of population-based colonoscopy screening may include complications induced by colonoscopy itself and by sedation, psychosocial distress, potential over-diagnosis and socioeconomic burden. In addition, harmful effect of colonoscopy may increase with age and comorbidity. As the adverse event risk in population-based colonoscopy screening may offset benefit of the screening colonoscopy, the adverse events associated with screening colonoscopy should be well managed and monitored. To adopt population-based colonoscopy screening, consensus for the risk and benefits of screening colonoscopy should be formed for its potential harms, patient preference, socioeconomic considerations, quality improvement of colonoscopy as well as its efficacy for CRC prevention. As the suboptimal colonoscopy quality is a major pitfall of population-based colonoscopy screening, adequate training and provider regulation for screening colonoscopists should be the first step to minimize the variation of quality between colonoscopists. Gastroenterologists should lead quality improvement, auditing, and training associated with colonoscopy in a population-based colonoscopy screening program.