Background We evaluated postoperative venous thromboembolism (VTE) chemical prophylaxis adherence to assess the preventability of VTEs. Methods A case-control study was performed using the 2011–2015 ACS-NSQIP single institution database. Cases were identified as patients who experienced postoperative VTE within 30 days following surgery. Controls were matched 2:1 on procedure, age, and BMI. Association between inpatient chemical prophylaxis adherence and postoperative VTE was evaluated with conditional logistic regression. Results Seventy-three cases were matched to 145 controls. Complete inpatient VTE chemical prophylaxis adherence did not differ between cases and controls (45.2% vs. 46.2%, p = 1.00). Odds of postoperative VTE increased if a patient's prophylaxis was interrupted (OR 6.34, 95% CI 1.82–22.13). However, 53.7% of instances of interrupted prophylaxis were medically justified by concern for bleeding, spine operation, or for additional upcoming procedure. Conclusions Nearly half of patients who experienced postoperative VTEs received appropriate guideline-driven care. Most interruptions in chemical prophylaxis were justified medically. This further questions the preventability of postoperative VTEs and the utility of this outcome as a valid measure of hospital quality.