Polymer nanofibers have become increasingly important for improvement of dissolution and bioavailability of poorly soluble drugs, representing a great challenge in pharmaceutical development. Here, we introduced a new concept of using amphiphilic polymers as fundamental excipients in electrospun nanofibers, which would improve drug solubilization and accelerate its release. Hydrophilic poloxamer-based nanofibers were developed as a novel drug delivery system for carvedilol. These nanofibers were electrospun from different liquid carvedilol dispersions, as carvedilol (nano) suspensions or ethanol solution. The electrospun products showed similar morphologies, but different mean fiber diameters (170-450 nm). Carvedilol dissolution rates from nanofibers were faster compared to its dissolution from polymer films. The electrospinning from ethanol solution resulted in the highest dissolution rate, since > 90% of the drug was dissolved in the first 5 min. The type of liquid medium significantly affects also the drug crystallinity. Thus, nanofibers produced from ethanol polymer solution showed no detectable crystalline carvedilol, whereas crystalline carvedilol form II or III was detected in the other nanofiber samples investigated. In a prolonged stability study (to 1 year), the potential of nanofibers to preserve the active ingredient in the initial non-crystalline form was demonstrated. Poloxamer-based nanofibers thus represent a promising formulation for immediate release and improved dissolution rates of poorly soluble drugs.