Despite the many advances in our understanding of cardiovascular diseases and how to diagnose and treat them, they are still the leading cause of death and disability in the Western World. Onset and progression of these diseases is due to interplay between pathologic flow conditions and vessel remodeling altering vessel geometries and composition. Advances in numerical simulation techniques and improvements in computational power have opened new avenues to investigate challenging pathological flow problems that underlie and characterize cardiovascular diseases. Mechanical heart valves (MHV) represent pathologic flow conditions common in cardiovascular prosthetic devices. Those result in platelet damage leading to thrombus formation and thromboembolism, which are major impidients to these devices. Numerical simulations were conducted to study platelet damage resulting by pathological flow patterns. The simulations included unsteady Reynolds averaged Navier Stoke (URANUS) and highly resolved direct numerical simulations (DNS) formulations. The thrombogenic potential of different MHV designs was evaluated from the sum of the product of stress and exposure time, determining platelet stress accumulation. Platelet cumulative damage due to repeated passages through the valve was also studied. Vulnerable plaques (VP) and abdominal aortic aneurysms (AAA) are examples of cardiovascular diseases that are driven by pathologic vessel geometries and compositions and compromised hemodynamics. Blood vessel integrity disruption and rupture in these diseases can lead to stroke, heart attack, and death. Numerical studies of their rupture risk was based on incorporating anisotropic vessel tissue material properties, and inclusion of calcification and intraluminal thrombus in patient specific geometries extracted from clinical imaging modalities, using fluid structure interaction (FSI) simulations to examine risk of rupture due to the contribution stresses and vessel tissue deformation.Advanced numerical tools that were developed and employed to study the conditions present in pathological blood vessels and in flows through prosthetic heart valves PHV are presented. These studies tackle highly complex cardiovascular disease processes using sophisticated engineering tools, adding to our understanding of biomechanical problems characterized by the interaction of blood flow with cardiovascular devices and pathological vessel geometries. This can aid optimizing the design of future cardiovascular devices and to augment clinical diagnostics of cardiovascular pathologies.