In May and June 2012, a national point prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use was conducted among French patients under home-based hospital care (HBHC). Data from 5,954 patients in 179 volunteer HBHC providers were collected. Prevalence of patients with at least one active HAI was 6.8% (95% confidence interval (CI): 6.1–7.4). Prevalence of those receiving at least one antimicrobial agent was 15.2% (95% CI: 14.3–16.1). More than a third (35.5%) of HAIs were HBHC-associated, 56% were imported from a healthcare facility and 8.5% of indeterminate origin. The main infection sites were urinary tract (26.6%), skin and soft tissue (17.6%), surgical site (15%), and pneumonia or other respiratory tract infections (13.5%). In multivariate analysis, three risk factors were associated with HBHC-associated infections: urinary catheter, at least one vascular catheter and a McCabe score 1 or 2. The most frequently isolated microorganism was Staphylococcus aureus (20.7%), 28.1% of them meticillin-resistant. Non-susceptibility to third-generation cephalosporins was reported in 25.3% of Enterobacteriaceae, of which 16.1% were extended spectrum beta-lactamase-producing strains. The most prescribed antimicrobials were fluoroquinolones (16.1%), and third-generation cephalosporins (14.5%). PPS may be a good start in HBHC to obtain information on epidemiology of HAIs and antimicrobial use.