Objective: The aim of this study was to investigate the effects of prayer and attachment to God on psychological well-being (PWB) in later life. Method: Using data from two waves of the nationwide Religion, Aging, and Health Survey, we estimate the associations between frequency of prayer and attachment to God at baseline with cross-wave changes in three measures of PWB: self-esteem, optimism, and life satisfaction. Results: Prayer does not have a main effect on PWB. Secure attachment to God is associated with improvements in optimism but not self-esteem or life satisfaction. The relationship between prayer and PWB is moderated by attachment to God; prayer is associated with improvements in PWB among securely attached individuals but not those who are insecurely attached to God. Discussion: These findings shed light on the complex relationship between prayer and PWB by showing that the effects of prayer are contingent upon one’s perceived relationship with God.