Various cranioplasty techniques exist for the reconstruction of cranial bone defects. Patient-specific implants can be produced in-house using a recently developed 3D printer-assisted cranioplasty technique. However, the resulting cosmetic outcomes from the patient's perspective are underreported. With our case series, we aim to present the clinical outcome, morbidity rate, patient-reported cosmetic results, and cost-effectiveness of patient-specific3D printer-assisted cranioplasty technique. This is a consecutive retrospective case series of adult patients undergoing cranioplasty using the patient-specific 3D printer-assisted technique. As primary endpoint, the functional outcome based on modified Rankin scale (mRS) at discharge and follow-up was assessed. A prospective telephone survey was conducted to collect and provide patient-reported outcomes. Thirty-one patients underwent patient-specific 3D printer-assisted cranioplasty, mostly to reconstruct frontotemporoparietal (61.3%) and frontotemporal defects with orbital involvement (19.4%). Good functional outcome (mRS ≤ 2) at discharge and during the last follow-up was achieved in 54.8% (n = 17) and 58.1% (n = 18) patients. Overall, the rate of clinically relevant surgery-related complications was 35.5% (n = 11). Postoperative epidural hematoma/collection (16.1%) and infections (12.9%) were the most frequent complications. Permanent morbidity occurred in one patient (3.2%) with postoperative acute ipsilateral vision loss after frontotemporal cranioplasty with orbital involvement. No surgery-related mortality occurred. The mean patient-reported cosmetic satisfaction score was 7.8 ± 1.5, with 80% of patients reporting satisfying or very satisfying cosmetic results. No significant differences were seen between the different defect localization regarding the cosmetic outcome. The mean manufacturing costs of a patient-specific 3D printer-assisted implant ranged from 748 to 1129 USD. Based on our case series, patient-specific 3D printer-assisted cranioplasty is cost-effective and leads to satisfying cosmetic results, especially in large defects and/or defects with complex geometry.