Knowledge on long-term population trends in crocodilians is essential to assess the effectiveness of conservation areas and to guide sustainable management practices. We studied changes in population size of spectacled (Caiman crocodilus) and black caimans (Melanosuchus niger) over a period of 17 yr at Mateococha, a black-water lake located in Cuyabeno Wildlife Reserve, western Amazonia, Ecuador. Using standardized spotlight counts and two mark–recapture surveys, we estimated the population abundance, body size structure, and sex ratio in 1994, 2004, and 2011. The maximum number of C. crocodilus recorded in 1994 (147 individuals; 33 individuals/kilometer [ind/km] of lakeshore) declined by 2004 to 94 individuals (21.1 ind/km) and by 2011 to 63 individuals (14.2 ind/km). The number of M. niger recorded was low but constant (5–7 individuals; 1.1–1.6 ind/km) throughout the study, suggesting that factors causing the decline in C. crocodilus were not related to the M. niger population trend. Large C. crocodilus adults (total length 150–220 cm) were frequent in 1994 but became rare in 2004 and 2011. The sex ratio of captured C. crocodilus was male-biased during all periods. The causes of the population decline are unknown, but available evidence suggests that illegal hunting and habitat degradation are likely culprits despite the protected status of the Cuyabeno Reserve. Our findings question the effectiveness of protected areas to ensure long-term survival of caiman populations in Ecuador.