Novel psychoactive substances (NPS) are compounds designed to mimic the effects of existing recreational drugs (classical psychoactive substances [CPS]), while eluding established legal frameworks. Little is known about their effects and potential harms, rendering the increasing number of NPS a challenge to policy makers and researchers alike. Quantitative studies on the motives underlying NPS use are limited, though understanding them is crucial for the design of effective harm prevention strategies. The present study therefore aimed to compare motivational patterns for NPS, CPS, and legal psychoactive substance (LPS) use. An online survey including questions about lifetime drug use, demographics, and motives for use was completed by 2,319 participants of which 1,967 consented and were 18 years or older. Data on lifetime use and endorsed motives are presented for 12 psychoactive substances classified into LPS (alcohol, nicotine), CPS (cannabis, MDMA/ecstasy, amphetamines, cocaine, psilocybin, LSD, ayahuasca), and NPS (synthetic cannabinoids, stimulant, and hallucinogenic) and compared between classes. Across substances, the most frequently endorsed motives were to feel euphoric (58.0%), enhance an activity (52.3%), and broaden consciousness (48.1%). Motives for use were found to differ by substance and gender, with coping-related reasons being more frequent among female participants compared to males who indicated to use for a broad range of reasons. Motivational patterns of CPS and NPS use were largely similar to their classical analogues, this was not the case for synthetic cannabinoids, which had as main endorsed motive getting intoxicated, indiscriminate of specific qualities. This information can feed into tailoring of educational campaigns and prevention strategies.