Purpose: To compare the accuracy of implant impressions using computer-aided impression-making technology and a conventional approach in a standardized setting in vitro, and to verify the effect of implant angulation (40 to 45 degrees) on the accuracy of digital and conventional impression-making procedures. Materials and methods: Four different edentulous mandibular reference models (RMs) were manufactured. Two straight (RM1); four straight (RM2); two straight and two tilted (RM3); and six straight (RM4) dental implants were placed, simulating four different clinical scenarios. The computer-aided impressions (n = 5 for each RM) were made using an intraoral scanner (IOS) (True Definition, 3M ESPE). Polyether (n = 5 for each RM) and vinyl polysiloxane (n = 5 for each RM) impression materials were utilized for the conventional approach. The collected data were analyzed in terms of trueness. The statistical analysis was performed using one-way analysis of variance (ANOVA). Results: The overall differences of interimplant distance, identified in mean values, were statistically significant among the different impression-making groups in RM1, RM3, and RM4. The data analyses of overall interimplant angle deviations yielded statistically significant differences in all four RMs. However, the deviations obtained with both impression-making approaches did not exceed an interimplant distance threshold of 100 µm, and an interimplant angle of 0.5 degrees, which seems to be clinically acceptable. Conclusion: Within the limits of this in vitro study, the accuracy of the computer-aided and conventional impression-making approaches for straight and tilted dental implants was comparable, and might be clinically considered for full-arch, multiple-implant restorations. However, further clinical studies are required to verify the feasibility of different IOSs (with and without scanning powder application), different implant systems, and multiple implant configurations.