Introduction. As surgical site infections (SSIs) after joint arthroplasty contribute to increased morbidity and mortality, they require further surgical intervention, prolonged hospitalisation, and antimicrobial treatment. The aim of our study is to examine the association between preoperative quality of life (QoL) and other predictive factors on the development of SSIs after primary arthroplasty. Methods. This is a prospective study that enrolled 56 patients with hip and knee primary osteoarthritis who underwent joint replacement. Data were collected from January to March 2017, including patient demographic characteristics, comorbidities, laboratory results, and perioperative clinical data. The patients’ QoL was evaluated preoperatively by applying the knee injury and osteoarthritis outcome score (KOOS) and the hip disability and osteoarthritis outcome score (HOOS) for total knee replacement (TKR) and total hip replacement (THR), respectively. A 5-year follow-up was conducted to assess the clinical status of the patients. Results. 66.1% of patients underwent TKR, with 4.9 ± 1.2 days of hospitalisation, 16% of them required autologous blood transfusion, while 33.9% of patients were treated with THR, with 5.7 ± 1 days hospitalisation and 36.8 of them required this type of transfusion. 16 patients were diagnosed with SSIs, with the older of them (>65 years old) presenting lower probability (odds ratio: 0.13, 95% CI: 0.03–0.62) requiring treatment with additional antibiotics, while revision surgery was performed in 3 of these cases, following periprosthetic joint infection (PJI). Overall preoperative QoL was not statistically associated with SSIs, but low QoL scores were associated with higher rates of SSIs and increased levels of postoperative pain (
p
= 0.009 < 0.05). Conclusions. The duration of each operation (>90 min), the length of hospitalisation (>4 days), and the presence of comorbidities including hypothyroidism and recurrent urinary tract infections were associated with a high risk for SSIs following arthroplasties. On the contrary, this study revealed no association between other comorbidities, including heart coronary disease, hypertension, and diabetes mellitus, with close monitoring of plasma glucose and SSIs. Moreover, the younger the patients, the more likely they were to require treatment with antibiotics. Overall, high QoL index scores were mainly accompanied by low rates of postoperative SSIs and pain.