Abstract Background There is a need for accurate and field-applicable instruments for the evaluation of the quality of anti-malarial drugs. The aim of this study was to determine the diagnostic accuracy of the NanoRam®, a handheld Raman spectrometer (RS), to identify anti-malarial drugs. Methods In total, 289 anti-malarial drugs collected in a randomized field survey in Gabon were evaluated. The samples were compared with authentic products as supplied by the official manufacturer. To determine the sensitivity and specificity of the handheld NanoRam® spectrometer in the identification of anti-malarial drugs, a two-gate reversed-flow design was applied. The standards for reporting of diagnostic accuracy studies (STARD) were followed. The index test was the handheld RS. The reference test standards were thin layer chromatography and high performance liquid chromatography with ultraviolet photo diode array detection. Results The sensitivity [95 % confidence interval (95 % CI)] and specificity of the RS to correctly identify an anti-malarial drug were 100 % (95 % CI 94.9–100 %) and 96 % (95 % CI 92.3–99.0 %), respectively. The RS could not differentiate between different batches of the same product or different manufacturers of the same product. Intra-observer agreement for 289 samples was 100 %. The average time to conduct the RS was 15 s per sample compared to 45 min per sample for TLC. Conclusion The handheld RS holds promise as an easy-to-use, quick and field-applicable instrument for the evaluation of quality of anti-malarial drugs, potentially empowering pharmacists, drug inspectors and medical regulatory authorities. Trial registration NTR4341 (Dutch Trial Registry)