Objectives: Work-related musculoskeletal disorders (MSD) are quite frequent in healthcare workers (HCWs), but data about MSD in home-based healthcare workers (HHWs) are lacking. In this study we describe the prevalence of MSD among Italian HHWs. Material and Methods: A case-control study was carried out among 300 random-selected female HCWs, the sample comprising 100 HHWs, 100 HCWs with a low exposure to patient handling (MAPO – Movimentazione e Assistenza Pazienti Ospedalizzati – Movement and Assistance of Hospital Patients index 0–5) and 100 HCWs with high exposure to patient handling (MAPO index ≥ 5.01). As a negative control group, 200 visual display unit workers were also randomly selected. Musculoskeletal disorder cases were collected using a standardized case definition. A multivariate logistic regression analysis was performed comparing the MSD prevalence in the 4 groups. Results: The overall prevalence of MSD was 17% in the reference group and 28.3% for HCWs. HHWs and HCWs with MAPO index ≥ 5.01 had similar prevalence of neck pain (9% and 11%, respectively), whereas lumbosacral pain prevalence was higher in the HHWs group (31%), with similar results in residential HCWs groups (21% in MAPO index 0–5 group and 25% in MAPO index ≥ 5.01 group). HCWs of group MAPO index ≥ 5.01 and HHWs showed the higher prevalence of upper limb complaints, with a prevalence of 20% and 10%, respectively. In multivariate regression analysis, prevalence of MSD complaints was quite similar in HHWs (adjusted odds ratio (OR_adj) = 2.335, 95% confidence interval (CI): 1.318–4.138) and in HCWs of the group MAPO ≥ 5.01 (OR_adj = 2.729, 95% CI: 1.552–4.797). Conclusions: The prevalence of MSD in the examined HCWs was relatively high, with HHWs appearing as a particularly high-risk group for lumbosacral back pain. In higher exposed HCWs, upper-limb symptoms were particularly frequent, probably reflecting the different tasks required to manage residential and homebased patients. In conclusion, this study reaffirms the high prevalence of MSD in HHWs, seemly similar to high-risk residential groups. Int J Occup Med Environ Health 2017;30(2):291–304