Background and aims On‐line drug markets flourish and consumers have high expectations of on‐line quality and drug value. The aim of this study was to (i) describe on‐line drug purchases and (ii) compare on‐line with off‐line purchased drugs regarding purity, adulteration and price. Design Comparison of laboratory analyses of 32 663 drug consumer samples (stimulants and hallucinogens) purchased between January 2013 and January 2016, 928 of which were bought on‐line. Setting The Netherlands. Measurements Primary outcome measures were (i) the percentage of samples purchased on‐line and (ii) the chemical purity of powders (or dosage per tablet); adulteration; and the price per gram, blotter or tablet of drugs bought on‐line compared with drugs bought off‐line. Findings The proportion of drug samples purchased on‐line increased from 1.4% in 2013 to 4.1% in 2015. The frequency varied widely, from a maximum of 6% for controlled, traditional substances ecstasy tablets, 3,4‐methylenedioxy‐methamphetamine (MDMA) powder, amphetamine powder, cocaine powder, 4‐bromo‐2,5‐dimethoxyphenethylamine (2C‐B) and lysergic acid diethylamide (LSD) to more than a third for new psychoactive substances (NPS) 4‐fluoroamphetamine (4‐FA), 5/6‐(2‐aminopropyl)benzofuran (5/6‐APB) and methoxetamine (MXE). There were no large differences in drug purity, yet small but statistically significant differences were found for 4‐FA (on‐line 59% versus off‐line 52% purity for 4‐FA on average, P = 0.001), MDMA powders (45 versus 61% purity for MDMA, P = 0.02), 2C‐B tablets (21 versus 10 mg 2C‐B/tablet dosage, P = 0.49) and ecstasy tablets (131 versus 121 mg MDMA/tablet dosage, P = 0.05). The proportion of adulterated samples purchased on‐line and off‐line did not differ, except for 4‐FA powder, being less adulterated on‐line (χ2 = 8.3; P < 0.02). Drug prices were mainly higher on‐line, ranging for various drugs from 10 to 23% higher than that of drugs purchased off‐line (six of 10 substances: P < 0.05). Conclusions Dutch drug users increasingly purchase drugs on‐line: new psychoactive substances in particular. Purity and adulteration do not vary considerably between drugs purchased on‐line and off‐line for most substances, while on‐line prices are mostly higher than off‐line prices.