The current paper examines the level of use of evidence and factors affecting the use of evidence by frontline maternal, newborn and child health (MNCH) and reproductive and child health (RCH) staff in practice decisions in selected health facilities in Ghana. Data on use of evidence and its correlates was collected from 509 frontline healthcare staff drawn from 44 health facilities in three regions in Ghana. Means were used to examine the level of use of evidence, whiles cross-tabulations and Partial Least Squares-based regression were used to examine factors associated with the use of evidence in practice decisions by frontline MNCH/RCH staff. The findings suggest a high level of use of evidence by frontline MNCH/RCH staff in practice decisions (score of 3.98 out of 5), albeit that evidence use is skewed towards the use of practice guidelines and policies. For the antecedents of evidence use, attitude had the highest score (3.99), followed by knowledge (3.8), access to evidence (3.77) and organizational structure (3.57), using a threshold of 5. The regression results indicate that attitudes and knowledge of frontline MNCH/RCH staff, organizational structure (strongest association), years of experience, being a male and working in a mission health facility are significantly positive correlated with evidence use, whiles working in a private health facility or in the post-natal clinic is negatively correlated with the use of evidence. We argue that any effort to improve the use of evidence by frontline MNCH/RCH staff in practice decisions should focus on improving attitudes and knowledge of staff as well as challenges related to the structure of the organisation. Given however that the score for attitude was relatively high, emphases to improve evidence use should be on access to evidence and organizational structure in particular, which had the lowest score even though it has the strongest association with the use of evidence. © 2022. The Author(s).