Data from the Swedish national health care registers were used to investigate the risk of CVD in a cohort of 41,362 men with prostate cancer (Pca) on androgen deprivation therapy (ADT) compared with an age-matched, PCa-free comparison cohort (n = 187,785). Over a period of 6 years, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months for GnRH agonist therapy of 1.91 (1.66 to 2.20), an HR of CVD with AA of 1.60 (1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (1.16 to 2.76) versus the comparison cohort.