Individuals with prolonged or frequent episodes account for a disproportionate share of the burden of depression. However, there are surprisingly few data on whether individuals at risk for developing chronic-intermittent depression (CID) as opposed to briefer, infrequent depressive episodes (time-limited depression [TLD]) can be distinguished before their first depressive episode. We followed a community sample of 465 never-depressed females on five occasions from age 14 to 20 years and examined whether 18 preonset clinical and psychosocial variables prospectively predicted CID. The CID group accounted for 40% of depressed cases but 84% of the cumulative time depressed in the sample. Participants with CID ( = 60) exhibited significantly higher preonset levels of 16 of the 18 risk factors than the never-depressed group ( = 315). The TLD group ( = 90) had significantly higher preonset levels of nine risk factors than never-depressed participants. Finally, the CID group had significantly higher levels of nine risk factors than the TLD group, five of which were similar in TLD and never-depressed participants. These findings indicate that differences between CID and TLD are evident before onset and suggest that the liability to CID may be both greater than, and somewhat different from, the liability to TLD. Moreover, they suggest that individuals at risk for a malignant course of depression can be targeted for prevention and early intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).