There is a widespread acceptance of information system (IS) strategic alignment. How and whether IS strategic alignment creates value especially in developing countries remains a major challenge for most banks. Additionally, alignment scope is often general making it difficult to identify specific important strategic alignment factors. We explored factors perceived to influence IS-innovation strategic alignment, their interrelationships, and consequential effects among six universal banks in Ghana. Primary data were obtained through interviews. The two-dimensional solution accounted for 85.4% of the total variance with P value of 0.000 indicating strong dependency in the data. The findings indicate IS and innovation of the banks are well aligned, and innovative performance is an output of successful IS-innovation alignment. Collaboration and IS strategic projects factors contributed strongly to the successful alignment.The findings provide bank managers with more reliable and actionable insights to determine the dimensions of alignment that contribute more or less to firm performance. 2011); however, alignment research had always centred on the entire IS strategy or organizational structure (Chan & Reich, 2007) with lingering questions of whether-and how-IS strategic alignment creates value (Queiroz, 2017). In developing countries, IS strategic alignment remains a major challenge for most banks (Labidi et al., 2016). Understanding factors that influence IS-innovation alignment can improve management effort of assessing and determining business value of IT and the dimensions of alignment that contribute more or less to firm performance. However, ISinnovation alignment remains largely unexplored among the universal banks in Ghana, especially, factors that influence IS-innovation alignment.Our major objective of the study then becomes exploring factors that are perceived to influence IS and innovation strategic alignment. In addition, the interrelationships and consequential effects of these perceived alignment factors are explored. Research questions developed to explore the alignment factors were administered through interviews.