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Introduction Khorana score (KS) stratifies patients into low, intermediate, and high risk groups for venous thromboembolism (VTE). We examined the generalizability of the KS to risk of VTE and association with mortality. Methods A retrospective cohort study was conducted at Mount Auburn Hospital, Cambridge, Massachusetts. Patients aged 18 years or older undergoing chemotherapy were included. All patients were evaluated for a six-month period. Primary study endpoints were VTE or mortality. Results Some 277 participants were included with a mean age of 63.95 (standard deviation, SD ± 12.47). The incidence proportion was 6.13% and a total of 17 VTE events were reported over a 2.5-year period. Compared to those with a low KS (0), those with a high KS (3 or above) had 6.4 times (p=0.032) while with an intermediate KS (1-2) had 2.6 times the odds of having a VTE event (p=0.22). Those who had a VTE had 4.03 times the odds of death compared to those who did not have a VTE (p=0.006). Compared to those with a low KS, those with a high KS had 5.7 times (p=0.02) the odds of six-month mortality and 5.04 odds (p=0.001) of mortality at any time. Conclusion High KS was associated with increased odds of VTE and mortality in our study.