Background: A family history of colorectal cancer (CRC) in first-degree relatives (FDRs) increases the risk of CRC. However, beyond rare hereditary CRC syndromes, the influence of family history on CRC survival remains uncertain. Methods: We conducted a pooled analysis of 5,010 incident CRC cases from 6 prospective cohort studies and 2 population-based case-control studies within the International Survival Analysis in CRC Consortium (ISACC). Cox proportional hazards models were used to estimate overall survival (OS) and CRC-specific survival (CSS) in relation to family history of CRC in FDRs, and number of affected FDRs, adjusting for age, gender, body mass index, smoking status, use of aspirin/non-steroidal anti-inflammatory drugs, history of screening endoscopy, stage at diagnosis, tumor location and study site. We conducted subgroup analyses by age, gender, tumor location and stage. Results: 819 (16.3%) patients reported a family history of CRC. There were 1,580 (31.5%) total deaths over a median follow-up time of 4.6 years, of which 1,046 (66.2%) were due to CRC. Individuals with a family history of CRC were more likely to have undergone screening endoscopy (p < 0.001), have proximal colon tumors (p = 0.04) and non-metastatic CRC (p = 0.003). Having a family history of CRC was not associated with OS [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.89-1.19] or CSS (HR 1.13; 95% CI 0.95-1.36) after multivariate adjustment. Compared to patients without a family history, those with ≥ 2 affected FDRs had a HR of 0.92 (95% CI 0.59-1.43) for OS, and HR of 0.98 (95% CI 0.55-1.76) for CSS. There was no association between age at diagnosis of the affected FDR with OS (p_trend = 0.47) or CSS (p_trend = 0.16). In subgroup analyses, family history was associated with worse CSS in individuals diagnosed at age ≤ 70 years (HR 1.45; 95% CI 1.11-1.89), and in patients with distal colon cancer (HR 1.45; 95% CI 1.03-2.04). Conclusions: Among CRC patients,family history is generally not associated with CRC survival. However, family history may be associated with worse prognosis in individuals diagnosed at age ≤ 70 years, and in patients with distal colon cancer, suggesting a possible distinct pathogenic mechanism underlying a common genetic predisposition.