Background To assess the impact of primary tumor resection (PTR) on survival and morbidity in incurable colorectal cancer. Methods Systematic literature review and meta-analysis to compare PTR versus primary tumor intact (PTI). Results Seventy-seven studies were included, reporting on 159,991 participants (94,745 PTR; 65,246 PTI). PTR improved overall survival (hazard ratio [HR] 0.59, P \ 0.0001; mean difference [MD] 7.27 months, P \ 0.0001), cancer-specific survival (HR 0.47, MD 10.80), and progression-free survival (HR 0.76, MD 1.67). Overall survival remained significantly improved during subgroup analysis of asymptomatic patients (HR 0.69, MD 3.86), elderly patients (HR 0.46, MD 7.71), patients diagnosed after 2000 (HR 0.62, MD 7.29), patients with colon (HR 0.58, MD 6.31) or rectal (HR 0.54, MD 6.88) primary tumor, patients undergoing resection of primary tumor versus nonresectional surgery (NRS) to treat primary tumor complications (HR 0.56, MD 8.72), and of studies with propensity score analysis (HR 0.65, MD 5.68). Overall survival per treatment strategy was: [PTI/chemotherapy] 14.30 months, [PTI/bevacizumab] 17.27 months, [PTR/chemotherapy] 21.52 months, [PTR/bevacizumab] 27.52 months. PTR resulted in 4.5% perioperative mortality and 22.4% morbidity (major adverse events 10.2%, minor 18.5%, reoperation 2.5%, intraabdominal collection/sepsis 2.2%). PTI had 21.7% morbidity (obstruction 14.4%, anemia 11.0%, hemorrhage 1.5%, perforation 0.6%, adverse events requiring surgery 15.8%). NRS resulted in 10.6% perioperative mortality and 21.7% morbidity (major 7.9%, minor 21.7%, reoperation 0.1%). Conclusions PTR in patients with incurable colorectal cancer results in a limited improvement of survival without a significant increase in morbidity. PTR should be considered by the multidisciplinary team on an individual patient basis.