A simple, sensitive and rapid high performance thin layer chromatographic (HPTLC) method has been developed and validated for quantitative determination of Milnacipran Hydrochloride (MIL) in bulk and formulations. The chromatographic development was carried out on HPTLC plates precoated with silica gel 60 F254 using a mixture of acetonitrile, water and ammonia (6:0.6:1.6) (v/v/v) as mobile phase. Detection was carried out densitometrically at 220 nm. The Rf value of drug was found to be 0.63 ± 0.02. The method was validated as per ICH guideline with respect to linearity, accuracy, precision, robustness etc. The calibration curve was found to be linear over a range of 100–1000 ng μL−1 with a regression coefficient of 0.999. The accuracy was found to be very high (99.12–100.87%). %RSD values for intra-day and inter-day variation were not more than 1.43. The method has demonstrated high sensitivity and specificity. The method was applied for compatibility studies also. The method is new, simple and economic for routine estimation of MIL in bulk, preformulation studies and pharmaceutical formulation to help the industries as well as researchers for their sensitive determination of MIL rapidly at low cost in routine analysis.