We illustrate the importance of environment-dependent surface energy changes in predicting the micronization of active pharmaceutical ingredients (APIs) in gas antisolvent precipitation (GASP) processes. This size-reduction scheme exploits compressed CO2(g) as antisolvent (AS) at near-ambient temperatures. Ordinary API-loaded solvents (often sprays) are contacted with dense CO2, and during CO2 uptake in an evolving expanding liquid API + solvent + CO2 solution droplet, particle nucleation (N) sets in, continuing along with growth (G) and, ultimately, coagulation. A rational method [due to Nielsen and Sohnel (J. Cryst. Growth 1971, 11, 233) and Mersmann (J. Oyst. Growth 1990, 102, 841)] is used to estimate the changing embryonic solid/ternary solution interfacial energy, gamma. We demonstrate the dramatic yield and crystal size distribution (CSD) consequences of surface energy evolution (SEE) by carrying out N/G calculations for the surrogate organic API: phenanthrene dissolved in representative well-mixed micrometer-sized toluene droplets (sprayed into 298 K CO2 for p < 60 bar). To solve the population balance partial differential equation, we exploit the method of characteristics. Our results demonstrate that assuming constant surface energy, sometimes reasonable for API precipitation via the rapid expansion of supercritical-CO2 solvent (i.e.: relatively dilute rapid expansion of a supercritical solution conditions), fails for GASP-process modeling. When the crystal growth kinetics are sufficiently rapid, SEE also modifies performance via the Gibbs Kelvin reduction of small particle growth rates. Rational yet tractable methods to incorporate both systematic effects in future design/optimization/parameter estimation calculations are suggested.