Intrinsic dissolution rate (IDR) has traditionally been determined from a constant surface area of a substance. Here we present an optofluidic single-particle intrinsic dissolution rate (SIDR) method, by means of which real-time determination of IDR from continuously changing effective surface areas of dissolving individual microparticles, is possible. The changing surface area of the individual microparticles is characterized through continuous random orientation 3D particle morphology characterization during the dissolution process. Using noninvasive optical monitoring and nonspecific image analysis, we determined IDRs of a diverse set of substances from individual pure-substance microparticles (14-747 μg) with an average relative standard deviation of 9.4%. A linear fit between SIDR and literature equilibrium solubility values (R(2) = 0.999) was achieved and kinetic solubility equivalent SIDRs were obtained, for all substances, in as little as 1 min. Such miniaturized methods could become valuable tools in drug discovery, by providing resource sparing higher quality data acquisition means to replace current high-throughput solubility methods.