SLCO1B1 variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. The authors conducted a retrospective chart review on 20,341 patients who had genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.4%) received pharmacotherapy that did not increase risks for SAMS. Providers were more likely to cancel simvastatin orders in response to CDS alerts if genotyping had been done prior to the first simvastatin prescription than after (94.1% vs 28.5%, respectively; p < 0.001). CDS significantly reduces simvastatin prescribing at doses associated with SAMS.