Background/Objectives: Muscle biopsies are requested for the workup of myopathy when less invasive workup is inconclusive. We set forth to build a multivariate model of preoperative testing to increase the odds of diagnostic and therapeutic yield of a muslce biopsy. Methods:A 5-year retrospective chart review of 106 patients who underwent muscle biopsy was performed to evaluate preoperative workup including: magnetic resonance imaging, electromyography, muscle strength testing and laboratory evaluation including creatine kinase level, lactate level, urine myoglobin, acetylcholinesterase antibody testing, genetic testing or use of steroids in the preoperative period using Student's two-tailed t-test, two-tailed Fisher's exact test and multivariate regression model. Results:We found an overall biopsy diagnostic pathologic yield of 47% and therapeutic yield of 88%. None of the variables reached a level of significance of p-value < 0.05 in univariate testing. In the multivariate model preoperative use of steroids and creatine kinase were the closest predictors of diagnostic and therapeutic yield but failed to reach statistical significance. Conclusions:The therapeutic impact of muscle biopsies appears to be much greater than the diagnostic pathologic yield and the therapeutic impact larger than previously reported when rigorously defined. We were unable to create a statistically significant preoperative predictive model for muscle biopsy diagnostic and therapeutic yield.