Purpose: To compare the adaptation of single metal-ceramic crowns (MCCs) fabricated with three different methods: lost-wax metal casting (LMC), milling of hard cobalt-chromium (HCC) blanks, and milling of soft presintered cobalt-chromium (SCC) blanks. Materials and Methods: In this double-blind parallel randomized clinical trial, 60 single MCCs were fabricated using three different methods. Adaptation of the copings was evaluated radiographically, visually, and microscopically. Data were compared among the three groups using the Kruskal-Wallis test, followed by the Dunn post hoc test, one-way ANOVA, and paired t test (α = .05). Results: Radiographic data showed that the frequency of crowns with no marginal discrepancy was significantly higher in the SCC group than the LMC group. Evaluation of marginal adaptation with an explorer revealed that crowns with excellent marginal adaptation had lower frequency in the LMC group than the HCC and SCC groups. In the silicone replica technique, the recorded data revealed no significant difference. Application of porcelain veneering did not affect the adaptation of the copings. Conclusions: The SCC and HCC groups showed better clinical outcomes compared to the LMC group. However, all MCCs fabricated with the LMC method, milling of HCC blanks, and milling of SCC blanks had acceptable clinical adaptation. Int J Prosthodont 2023;36:581–587.