BACKGROUND: Methamphetamine misuse affects 27 million people worldwide and is associated with cardiovascular disease (CVD); however, risk factors for CVD among users have not been well studied. METHODS AND RESULTS: We studied hospitalized patients in California, captured by the Healthcare Cost and Utilization Project database, between 2005 and 2011. We studied the association between methamphetamine use and CVD (pul-monary hypertension, heart failure, stroke, and myocardial infarction). Among 20 249 026 persons in the Healthcare Cost and Utilization Project, 66 199 used methamphetamines (median follow-up 4.58 years). Those who used were more likely younger (33 years versus 45 years), male (63.3% versus 44.4%), smoked, misused alcohol, and had depression and anxiety compared with nonusers. Methamphetamine use was associated with the development of heart failure (hazard ratio [HR], 1.53 [95% CI, 1.45–1.62]) and pulmonary hypertension (HR, 1.42 [95% CI, 1.26–1.60]). Among users, male sex (HR, 1.73 [95% CI, 1.37– 2.18]) was associated with myocardial infarction. Chronic kidney disease (HR, 2.38 [95% CI, 1.74– 3.25]) and hypertension (HR, 2.26 [95% CI, 2.03– 2.51]) were strong risk factors for CVD among users. When compared with nonuse, methamphetamine use was associated with a 32% significant increase in CVD, alcohol abuse with a 28% increase, and cocaine use with a 47% increase in CVD. CONCLUSIONS: Methamphetamine use has a similar magnitude of risk of CVD compared with alcohol and cocaine. Prevention and treatment could be focused on those with chronic kidney disease, hypertension, and mental health disorders.