Weakly basic drugs are predisposed to order of magnitude decreases in solubility and dissolution as pH increases from 1 to 7 along the gastrointestinal tract. Such behavior is known to be detrimental to drug absorption. The work presented here shows how cocrystals of basic drugs with acidic coformers can mitigate these negative effects. Cocrystals of ketoconazole (KTZ) with adipic, fumaric, and succinic acids exhibit a parabolic solubility dependence on pH such that with increasing pH, solubility decreases, reaches a minimum, and increases. Cocrystals exhibit pHmax values between 3.6 and 3.8, above which they generate supersaturation with respect to drug. Cocrystal supersaturation index (SA), defined as Scocrystal/Sdrug, changes from 1 (pHmax) to 10–30 (pH 5) to 800 – 3,000 (pH 6.5). SA represents the driving force for cocrystal conversion to the less soluble drug during dissolution. SA is not expected to be equal to the observed supersaturation, but it is of great value to classify cocrystals in terms of their risk of conversion. Cocrystal dissolution behavior was analyzed in terms of Cmax, σmax (maximum KTZ concentration and supersaturation), AUCdiss (KTZ concentration area under the curve during dissolution-precipitation), and SA. The three cocrystals studied achieved σmax values between 5 and 15 and sustained supersaturation for 1 to 3 h, resulting in AUCdiss advantage over drug in the range of 2 to 12. SA values as high as 800 were associated with enhanced drug exposure. SA of 3,000 led to limited exposure, very rapid conversion, and no measurable supersaturation. Since cocrystals may be more soluble than needed and/or too soluble to be developed, there is great value in recognizing the relationship between supersaturation threshold, cocrystal solubility, and SA. This becomes more important as cocrystal SA is dependent on pH and other environmental conditions.