Purpose: To assess the impact of prosthetic rehabilitation on quality of life (QoL) in patients with cleft lip and palate (CLP) and in edentulous patients with implant-supported complete dentures (ICD). Materials and Methods: CLP (n = 20) and ICD (n = 26) patients completed the Oral Health Impact Profile (OHIP-14). Nine patients with an OHIP-14 score above the 75th percentile were interviewed. Data were interpreted using inductive content analysis and triangulation. Results: ICD patients scored higher than CLP patients in overall OHIP-14 score and in most domains (P .05). After rehabilitation, CLP patients reported improvement in psychosocial functions but worsening in physical functions. ICD patients had improvement in all domains, but were less satisfied. Conclusion: The mixed-methods study design can detect the origins and interactions of factors in treated patients with complex problems.