(1) Background: There is limited evidence related to the efficacy of advanced clinical decision support systems (CDSS) on the quantity of high-quality clinical recommendations in a pharmacy-related medication therapy management (MTM) setting. The study aimed to assess the effect of an advanced CDSS on the quantity of relevant clinical pharmacist recommendations in a call center MTM setting. (2) Methods: This pre-test/post-test with comparator group study compared clinical skills assessment scores between certified MTM pharmacists in March 2020. A Wilcoxon Signed Rank test assessed the difference between pre- and post-test scores in both groups. (3) Results: Of 20 participants, the majority were less than 40 years old (85%) with a Doctor of Pharmacy degree (90%). Nine were female. Intervention group participants had less than three years of experience as a pharmacist. The control group had less than three years (40%) or seven to ten years (40%) of experience. There was a significant increase in intervention group scores between pre- (median = 3.0, IQR = 3.0) and post-test segments (median = 6.5, IQR = 4.0, = 0.02). There was no significant change between control group pre- and post-test segments ( = 0.48). (4) Conclusion: Pharmacist exposure to an advanced CDSS was associated with significantly increased quantity of relevant clinical recommendations in an MTM pharmacy setting.