Diagnostic criteria of analgesic nephropathy with well-defined sensitivity and specificity are not available. During a 2-year period all new patients (n = 273) starting renal replacement therapy in 13 Belgian dialysis units were investigated aiming to select diagnostic criteria of analgesic nephropathy with acceptable performance. Using several interview techniques, a history of analgesic abuse was found in 31% of the patients. Analgesic abusers presenting a clear non-analgesic-related renal diagnosis were excluded from analysis (n = 25). Comparing the remaining abusers (n = 60) and patients without a history of analgesic abuse (n = 188) it was found that renal imaging investigations (sonography plus tomography), showing a decrease in length combined with bumpy contours of both kidneys, presented a sensitivity of 90% and a specificity of 95%. The additional finding of signs of renal papillary necrosis resulted in an overall sensitivity of 72% and a specificity of 97%, giving a positive predictive value of 92%. Other signs frequently mentioned in the literature (hypertension, anaemia, sterile pyuria, bacteriuria, proteinuria) showed insufficient sensitivity and/or specificity to be of help for diagnosing analgesic nephropathy in end stage renal failure (ESRF) patients starting renal replacement therapy.