Patients with single-sided deafness (SSD) lack the ability localize sound sources and have difficulty with speech-in-noise hearing. In addition, there is ahigh prevalence of tinnitus distress. These problems may result in reduced health-related quality of life (HRQoL) and psychological comorbidities. This study aimed to investigate the influence of treatment with a cochlear implant (CI) on HRQoL, tinnitus distress, psychological comorbidities, and audiological parameters in SSD patients. This retrospective study included 20patients with postlingually acquired SSD (13women, 7men, mean age 57.0years). Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire (NCIQ) and the Medical Outcome Study Short Form36 Survey (SF-36). Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ), psychological comorbidities were evaluated with validated questionnaires, and speech perception and hearing ability were measured with validated speech tests. Postoperatively, the mean total NCIQ score (p < 0.0001) and four subscores improved significantly, as did tinnitus distress (p < 0.05). Anxiety symptoms (Generalized Anxiety Disorder questionnaire, GAD-7) decreased significantly after CI. Speech perception improved significantly, particularly "hearing with background noise" (p < 0.05, Oldenburg Inventory, OI) and "localization" (p < 0.001, OI), as well as the Oldenburg Sentence Test (OlSa) scores for with vs. without CI when speech was presented from the SSD side and noise was presented from the normal hearing side (SSSDNNH; p < 0.005). CI in SSD patients is apowerful procedure to improve HRQoL, reduce tinnitus distress, and improve psychological comorbidities. Additionally, it is beneficial for hearing improvement, particularly in noise and for directional hearing.