A method is provided for determining a worst-case single cycle setup time between a first and second clock domain. First, an offset time of a second clock domain with respect to a first clock domain is normalized. A base period of the first clock domain and the second clock domain is then obtained. Next, a first greatest common denominator (GCD) shared by the first and second clock domains and the normalized second clock domain offset time is factored. Then, a reduced offset time and a reduced offset time size factor are substituted into an expression representing a relationship between the first and second clock domains. A second GCD shared by the first and second clock domains is factored from the expression and a modulus value of the reduced offset time and the second GCD is computed. Based on the modulus value, the worst-case single cycle setup time is computed.