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Background: On May 6, 1887 at a meeting of the West London Medico-Chirurgical Society, original observations attributed to D. H. Goodsall described an association between the secondary (external) sinus opening and the location of the primary (internal) opening of an anal fistula: posterior external sinuses had a midline origin and anterior external sinuses took a straight path to their internal origin-eponymously known as Goodsall's Rule. However, over the last century, published reports support the midline as the primary (internal) origin of all anal fistulas, thus challenging the predictive accuracy of Goodsall's Rule and prompting this expansive review., Methods: A literature search was performed for studies describing the relationship between the secondary (external) opening and the primary (internal) opening of anal fistulas, including recent reports of the positive predictive value (PPV) of Goodsall's Rule. The studies were evaluated to determine the validity of Goodsall's observations., Results: The midline was the dominant, primary (internal) opening site of all anal fistulas with up to 95% accuracy. Goodsall's Rule was inaccurate when applied to anal fistulas with an anterior off-midline external sinus opening which tend to mirror posterior off-midline external sinuses and curve to a midline origin, rather than take a straight course to a primary (internal) opening, as predicted by Goodsall. Use of the Midline Rule had superior predictive accuracy, reflected in an increase in overall PPV of the location of the primary (internal) origin from 49% using Goodsall's Rule to 71% using the Midline Rule (57-62% for men, 31-90% for women)., Conclusions: Goodsall's Rule falls short in predicting the natural course of anal fistulas with an anterior off-midline external sinus opening, especially for women. Given the increased risk of fecal incontinence related to surgical intervention for anterior-based anal fistulas, especially in women, dependence on Goodsall's Rule to guide the surgeon may result in "disastrous consequences". The preponderance of evidence over the last century favors the Midline Rule as a more accurate predictor of the true and natural course of anal fistulas, regardless of the location of the external sinus opening.