A new library of E- and C-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives has been synthesized through a straightforward protocol from commercially available BODIPY complexes, and a systematic study of the photophysical properties and laser behavior related to the electronic properties of the B-substituent group (alkynyl, cyano, vinyl, aryl, and alkyl) has been carried out. The replacement of fluorine atoms by electron-withdrawing groups enhances the fluorescence response of the dye, whereas electron-donor groups diminish the fluorescence efficiency. As a consequence, these compounds exhibit enhanced laser action with respect to their parent dyes, both in liquid solution and in the solid phase, with lasing efficiencies under transversal pumping up to 73 % in liquid solution and 53 % in a solid matrix. The new dyes also showed enhanced photostability. In a solid matrix, the derivative of commercial dye PM597 that incorporated cyano groups at the boron center exhibited a very high lasing stability, with the laser emission remaining at the initial level after 100 000 pump pulses in the same position of the sample at a 10 Hz repetition rate. Distributed feedback laser emission was demonstrated with organic films that incorporated parent dye PM597 and its cyano derivative. The films were deposited onto quartz substrates engraved with appropriate periodical structures. The C derivative exhibited a laser threshold lower than that of the parent dye as well as lasing intensities up to three orders of magnitude higher.