Purpose: To compare the effects of fabricating methods of custom monoblock mandibular advancement devices (MADs) on usability and efficacy in patients with mild and moderate obstructive sleep apnea (OSA). Materials and Methods: Digitally fabricated custom MADs (dMADs) were produced for 11 OSA participants who had previously used conventionally fabricated custom MADs (cMADs). The participants answered a modified usability questionnaire for both MADs, and the average scores that were given to the questionnaire were evaluated by age, sex, and body mass index (BMI), and the scores of cMADs and dMADs were compared. After 6 months of usage of each MAD, the apnea-hypopnea index (AHI), mean and lowest oxygen saturations, and total sleep time were measured for efficacy assessment. Data were analyzed with Cronbach's alpha, Mann-Whitney U, Kruskal-Wallis, Wilcoxon signed-rank, one-way repeated measures analyses of variance, and Bonferroni tests (α = 0.05). Results: Cronbach's alpha was found at 0.834 and 0.722 for the conventional and digital questionnaires, respectively. The usability scores of the dMADs were significantly higher than those of cMADs (p = 0.013). There was no difference in usability scores in terms of sex or BMI (p > 0.05). No statistically significant difference was found for cMAD (p = 0.113) among age groups; however, there was a significant difference for dMAD (p = 0.046). The AHI, mean, and lowest oxygen saturation values were significantly affected by MAD usage (p < 0.001). However, total sleep time values did not differ after the MAD treatments (p > 0.05). Significantly lower AHI and significantly higher lowest oxygen saturation values were observed with dMAD, while both appliances led to similar results for mean oxygen saturation and total sleep time values (p > 0.05). Conclusions: Participant usability scores were higher for digitally manufactured MADs than conventionally manufactured MADs. However, both conventional and digital MADs were found effective in decreasing the AHI levels and increasing the mean and lowest oxygen saturation values of the participants.