Tadalafil works on the PDE5 enzyme in the lungs to relax the blood vessels. This will increase the supply of blood to the lungs and reduce the workload of the heart. This medicine is available only with your doctor's prescription. . How long does it take to work? Tadalafil usually starts to work within 30 to 60 minutes. If you're taking it for erectile dysfunction, it's triggered by sexual stimulation, so you need to be aroused for it to work.