OBJECTIVE To investigate the incidence of new-onset diabetes mellitus (NODM) and of worsening glycaemic control in established DM after starting androgen-deprivation therapy (ADT) for prostate cancer, as ADT is associated with altered body composition, potentially influencing insulin sensitivity. PATIENTS AND METHODS We retrospectively reviewed patients receiving ADT for prostate cancer at our institution between January 1989 and July 2005; those with incomplete information and those receiving only neoadjuvant ADT were excluded. Variables examined included age, race, body mass index (BMI), pretreatment prostate-specific antigen, Gleason sum, clinical stage, ADT type (medical vs surgical) and schedule (continuous vs intermittent), presence of pre-existing DM, serum glucose and glycosylated haemoglobin (HbA1c) levels before and after ADT, and receipt of vitamin D or bisphosphonate supplementation. Data were analysed statistically and P < 0.05 considered to indicate significance. RESULTS In all, 396 patients (median age 73.2 years; median BMI of 26.7 kg/m(2) at ADT initiation) were analysed. Of these, 59.1% were African-American and 40.9% were Caucasian/other. At a median follow-up of 60.1 months, 36 (11.3%) patients developed NODM. In 77 patients with pre-existing DM, there was an increase of >/=10% in serum HbA1c or fasting glucose levels in 15 (19.5%) and 22 (28.6%), respectively. On multivariate analysis, a BMI of >/=30 kg/m(2) was associated with an increased risk of developing NODM (odds ratio 4.65, P = 0.031). Receipt of vitamin D had a protective effect (odds ratio 5.75, P = 0.017). CONCLUSIONS Patients receiving ADT for prostate cancer with or with no history of DM should have routine surveillance of glycaemic control, particularly when their BMI is >/= 30 kg/m(2), with appropriate preventive and treatment measures.