Background: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk. Objective: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke. Methods: In a multi-ethnic cohort of 5879 U.S. adults (45–84 years), who were free of CVD at baseline, protein intake was assessed at baseline (2000–2002) using a validated 120-item food frequency questionnaire. Two different aspects of protein diversity were assessed including count (number of protein food consumed at least once/week) and dissimilarity (diversity of the attributes of the protein sources consumed). Relationships with incident CVD outcomes through 2019 were assessed using Cox proportional hazards models adjusting for sociodemographic, lifestyle, and comorbidity factors. Results: During 83,430 person-years, 1045 CVD cases were identified, including 668 CHD and 332 stroke cases. In multivariable models, we found no significant associations between protein intake, overall and by food source, with incident CVD, CHD, or stroke. Protein count, but not protein dissimilarity, was weakly associated with CVD risk. We found no significant associations between diversity of consumption of animal or plant food source and CVD outcomes. Conclusions: Our findings suggest protein consumption may not significantly impact CVD risk in middle-aged adults.