Objective: To determine factors associated with nonelective PICC removal and complications. Study design: Overall, 1234 PICCs were placed in 918 hospitalized infants <45 weeks postmenstrual age. Outcomes studied include nonelective PICC removal (removal prior to completion of therapy) and line complications. Univariate and multivariate mixed-effects logistic regression analyses were conducted to evaluate the associations between potential predictor variables and clinical outcomes Results: Nonelective PICC removal occurred in 28.4% and complications in 34.4% of infants. Nonelective removal (p < 0.001) and complications (p = 0.006) occurred more often with upper than lower extremity PICCs. Malposition in the first 72 h (p = 0.0009) and over time (p = 0.0003) were more common in upper extremity PICCS; however, upper extremity PICCs were associated with a decreased incidence of phlebitis, edema, and perfusion changes (p = 0.03). Conclusions: Approximately one-third of PICCs were associated with complications. When feasible, lower extremity PICCs should be placed as they may be associated with fewer complications.