Recently, a high proportion of patients with late-stage Trypanosoma brucei gambiense trypanosomiasis, who had been treated with melarsoprol in some disease-endemic areas, subsequently relapsed. To determine whether the frequency of postmelarsoprol relapses increased over time, we reviewed data from 2,221 trypanosomiasis patients treated with melarsoprol during this period in Nioki, Democratic Republic of Congo, from 1982 to 2001. The frequency of relapses was 5.6%(31/553), 6.8%(35/512), 4.5%(18/398), 11.4%(34/299), and 5.0%(17/343) for those treated from 1982 to 1985, 1986 to 1989, 1990 to 1993, 1994 to 1997, and 1998 to 2001, respectively. The higher frequency of relapses in 1994 to 1997 was associated with an incremental dosage regimen of melarsoprol. In multivariate analysis, after adjustment for treatment regimen, sex, residence, and trypanosomes in cerebrospinal fluid, postmelarsoprol relapses did not increase in Nioki, perhaps because 1) little drug pressure exists; 2) subtherapeutic doses have rarely been administered; 3) little potential exists for the preferential transmission of melarsoprol-resistant strains.