OBJECTIVES Primary tumor resection (PTR) is recommended for patients with unresectable stage Ⅳ colorectal cancer (CRC) who present with symptoms related to their primary tumor (eg, obstruction, perforation,significant bleeding).However, the survival benefit of PTR for asymptomatic patients is controversial.We investigated the change in PTR rates and the contribution of PTR to survival in patients with unresectable stage Ⅳ CRC over the past two decades in the United States.METHODS A retrospective cohort study using data from the National Cancer Institute's Surveillance,Epidemiology, and End Results (SEER) CRC registry.Clinicopathological factors and long-term survival were compared for 44 514 patients diagnosed with unresectable stage Ⅳ CRC from January 1, 1988, through December 31, 2010, who had or had not undergone PTR.PTR rates and median survival times were calculated for each year of diagnosis.Multivariable Cox regression and the instrumental variable method were used to identify independent factors for survival.RESULTS Of the 44 514 patients with unresectable stage Ⅳ CRC, 27 931 (62.7%) had undergone PTR.The annual rate of PTR decreased from 74.4% to 50.2% diagnosed in 1988 and 2010, and the median overall survival increased for both PTR and non-PTR patients.Instrumental variable analvses revealed that PTR was associated with better overall (HR 0.50, 95% confidence interval [CI] 0.49-0.52), cancer-specific (HR 0.50, 95% CI 0.49-0.51), and other-cause (HR 0.54, 95% CI 0.49-0.59) survival.CONCLUSIONS PTR was associated with better overall, cancer-specific, and other-cause survival of patients with unresectable stage Ⅳ CRC.