Two-sided assembly lines are often designed to produce large-sized products, such as automobiles, trucks and buses. In this type of production line, both left-side and right-side of the line are used in parallel. In all studies on two-sided assembly lines, sequence-dependent setup times have not yet been considered. However, in real life applications, setups may exist between tasks. Performing a task directly before another task may influence the latter task inside the same station, because a setup for performing the latter task may be required. Furthermore, if a task is assigned to a station as the last one, then it may cause a setup for performing the first task assigned to that station since the tasks are performed cyclically. In this paper, the problem of balancing two-sided assembly lines with setups (TALBPS) is considered. A mixed integer program (MIP) is proposed to model and solve the problem. The proposed MIP minimises the number of mated-stations (i.e., the line length) as the primary objective and it minimises the number of stations (i.e., the number of operators) as a secondary objective for a given cycle time. A heuristic approach (2-COMSOAL/S) for especially solving large-size problems based on COMSOAL (computer method of sequencing operations for assembly lines) method is also presented. An illustrative example problem is solved using 2-COMSOAL/S. To assess the effectiveness of MIP and 2-COMSOAL/S, a set of test problems are solved. The computational results show that 2-COMSOAL/S is very effective for the problem.