Recent findings have found that the influenza vaccine induces changes in the immune system in favor of antitumor cytotoxicity. The aim of our study was to investigate if an influenza vaccine given in the postoperative period decreased overall and cancer-specific mortality in patients undergoing curative surgery for solid cancers. We conducted a registry-based national observational study in Denmark in the period January 1, 2010 to December 31, 2015 with a follow-up period of 3 years starting from 180 days after surgery. Patients with solid cancers undergoing curative surgery were included. The primary outcome was overall mortality. The secondary outcome was cancer-specific mortality. A total of 21 462 patients were included in the study with 2557 patients receiving an influenza vaccine within 6 months after surgery. In a Cox regression model, a decrease in overall mortality (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.81-0.99, P =.03) and cancer-related mortality (HR = 0.82, 95% CI = 0.71-0.93, P =.003) was found among patients given a vaccine vs patients never receiving a vaccine. In a predefined subgroup of patients receiving a vaccine within 30 days after surgery, a decrease in overall mortality (HR = 0.82, 95% CI = 0.72-0.94, P =.007) and cancer-specific mortality (HR = 0.70, 95% CI = 0.53-0.91, P =.009) was found. No association was evident in patients receiving the vaccine after 30 days to 6 months after surgery (overall mortality: HR = 0.96, 95% CI = 0.86-1.07, P =.46); cancer-specific mortality: HR = 0.88, 95% CI = 0.76-1.03, P =.12). These findings must be investigated in larger clinical trials where both immunological biomarkers and survival outcomes are included.