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Objective: Drug dependency has been typified as a persistent relapsing disorder. Overall, 65% of people with substance use disorders relapse within one year after treatment. Recent interventions have focussed on contextually relevant relapse prevention strategies. This study explored relapse prevention strategies utilised by patients recovering from polysubstance use disorders one year after treatment at a Psychiatric Rehabilitation Unit in Ghana. Methods: The study adopted a descriptive phenomenology design and was conducted at the Psychiatric Rehabilitation Unit of the Regional Hospital, Sunyani, Ghana. A purposive sample of 15 patients recovering from poly-substance use disorders were recruited. Data were collected through in-depth interviews with a semistructured guide and analysed using the content analysis procedures. Results: Five key themes emerged from the analysis of the data that described participants’ relapse prevention strategies. These include clinical strategies, selfinitiated tactics, spirituality and religious engagements, communalism and social support network. Conclusions: The evidence from this study supports a multilevel treatment strategy for patients with poly-substance disorders. We found that a combination of clinical, individual and contextual factors significantly contribute to relapse prevention efforts in the Ghanaian context. Clinicians and treatment services should explore, evaluate, strengthen and incorporate these emerging themes into their relapse prevention interventions protocols