The recent developments in liquid chromatography (LC) are mainly dedicated to both system miniaturization (micro-, capillary-, and nano-LC) and analysis time decrease (fast-, and ultra-fast-LC). For the latter, several strategies can be used, and high temperature liquid chromatography (HTLC) seems very promising and easy to implement, especially in miniaturized system. In LC, the evaporative light scattering detector (ELSD) is considered an attractive alternative to conventional detector such as UV-vis due to its versatility and quasi-universality. Therefore, the compatibility of ELSD with mu-LC and mu-HTLC was investigated for several pharmaceutical compounds of interest. The nebulization process appeared to be the most critical parameter for performing the coupling and maintaining an efficient separation. Therefore, appropriate modifications in the nebulization cell geometry were brought to make ELSD fully compatible with mu-LC. The impact of optimized nebulization cell on chromatographic performance was evaluated in terms of efficiency and sensitivity. Finally, highly efficient, sensitive and fast separations of pharmaceutical drugs were performed with both techniques and the customized nebulization cell design.