Background The association between cancer and venous thromboembolism (VTE) in producing adverse clinical outcomes requires further investigation. Methods In the Swiss Venous ThromboEmbolism Registry (SWIVTER), we compared adverse clinical outcomes between 493 patients with cancer-associated VTE and 1,569 VTE patients without cancer, and identified independent predictors of 90-day mortality. Results Among cancer patients, 351 (71%) had active disease at the time of VTE diagnosis and 232 (47%) had metastatic disease. Cancer patients more frequently had asymptomatic VTE (13 vs. 4%; p < 0.001), iliofemoral deep vein thrombosis (42 vs. 32%; p = 0.017), and upper extremity deep vein thrombosis (16 vs. 7%; p < 0.001). Cancer was associated with an increased risk of cumulative 90-day mortality (13.0 vs. 2.2%; hazard ratio [HR], 6.27; 95% confidence interval [CI], 4.13-9.50; p < 0.001), recurrent VTE (4.7 vs. 2.3%; HR, 2.05; 95% CI, 1.21-3.45; p = 0.007), and bleeding requiring medical attention (5.7 vs. 3.3%; HR, 1.80; 95% CI, 1.13-2.86; p = 0.013). Among cancer patients, the strongest factor associated with mortality was metastatic disease (HR, 4.86; 95% CI, 2.68-8.81; p < 0.001), whereas it was pulmonary embolism among noncancer patients (HR, 4.96; 95% CI, 1.50-16.45; p = 0.009). Symptomatic as compared with asymptomatic VTE predicted neither mortality (12.6 vs. 15.9%; HR, 0.76; 95% CI, 0.39-1.49; p = 0.42) nor recurrent VTE (4.7 vs. 4.8%; HR, 0.98; 95% CI, 0.29-3.31; p = 0.98) in cancer patients. Conclusion In SWIVTER, early mortality of cancer-associated VTE was mainly driven by the extent of cancer disease and not by VTE symptoms or severity.