The perioperative use of certain medication may influence the risk of developing a periprosthetic joint infection (PJI). Inhaled corticosteroids (ICSs) and cardiovascular drugs are widely used against pulmonary and cardiovascular diseases. While oral corticosteroids and anticoagulants have been shown to increase the risk of developing PJI, this is not clear for ICSs. In contrast, some cardiovascular drugs, such as amlodipine, nifedipine and statins, have been documented to show an antimicrobial effect, suggesting a synergistic effect with antibiotics in the treatment of (multi-resistant) microorganisms. We performed a case–cohort study to assess the association between the occurrence of PJI after THA and the use of inhaled corticosteroids, anticoagulants, or previously mentioned cardiovascular agents. In a cohort of 5512 primary THAs, we identified 75 patients with a PJI (1.4%), and randomly selected 302 controls. A weighted Cox proportional hazard regression model was used for the study design and to adjust for potential confounders (age, sex, smoking, and cardiovascular/pulmonary disease). We found ICS use (HR 2.6 [95% CI 1.1–5.9]), vitamin K antagonist use (HR 5.3 [95% CI 2.5–11]), and amlodipine use (HR 3.1 [95% CI 1.4–6.9]) to be associated with an increased risk of developing PJI after THA. The effect remained after correction for the mentioned possible confounders. The underlying diseases for which the medications are prescribed could also play a role in the mentioned association; we believe, however, that the usages of ICSs, vitamin K antagonists and amlodipine appear to be potential modifiable risk factors for PJI, and therefore have to be questioned during preoperative screening and consultation.