Venous thromboembolism (VTE) prophylaxis has been suggested for patients who underwent total join arthroplasty (TJA). However, the morbidity of surgical site complications (SSC) and periprosthetic joint infection (PJI) has not been well evaluated. We aimed to evaluate the impact of VTE prophylaxis on the risk of early postoperative SSC and PJI in a Taiwanese population. We retrospectively reviewed 7511 patients who underwent primary TJA performed by a single surgeon from 2010 through 2019. We evaluated the rates of SSC and PJI in the early postoperative period (30-day, 90-day) as well as 1-year reoperations. Multivariate regression analysis was used to identify possible risk factors associated with SSC and PJI, including age, sex, WHO classification of weight status, smoking, diabetes mellitus (DM), rheumatoid arthritis(RA), Charlson comorbidity index (CCI), history of VTE, presence of varicose veins, total knee or hip arthroplasty procedure, unilateral or bilateral procedure, or receiving VTE prophylaxis or blood transfusion. The overall 90-day rates of SSC and PJI were 1.1% (N = 80) and 0.2% (N = 16). VTE prophylaxis was a risk factor for 90-day readmission for SSC (aOR: 1.753, 95% CI 1.081–2.842), 90-day readmission for PJI (aOR: 3.267, 95% CI 1.026–10.402) and all 90-day PJI events (aOR: 3.222, 95% CI 1.200–8.656). Other risk factors included DM, underweight, obesity, bilateral TJA procedure, younger age, male sex and RA. Pharmacological thromboprophylaxis appears to be a modifiable risk factor for SSC and PJI in the early postoperative period. The increased infection risk should be carefully weighed in patients who received pharmacological VTE prophylaxis.