Psychotherapy is an interpersonal process of collaboration toward specified treatment goals. The therapeutic alliance is well established as an important factor of psychotherapeutic change. However, the experience of distress in social interactions, commonly referred to as interpersonal problems, might be interfering with the collaborative process during psychotherapy. This study systematically reviews the literature and obtains an estimate of the relationship between pretreatment interpersonal problems and the quality of the therapeutic alliance. Overall, 27 studies with 48 correlation coefficients were included in the final analysis. Due to the nested structure of the data, a three-level meta-analytic approach with a restricted maximum likelihood estimator was applied. Alliance assessment phase, alliance rater, alliance measure instrument, and treatment type were tested as potential moderators. Heterogeneity and publication bias test were performed. The meta-analysis showed a small, but significant negative relationship between interpersonal problems at the beginning of psychotherapy and subsequent therapeutic alliance (r = −.12, SE = .02, 95% CI −.16, −.08, p < .001, d = −.27). Only alliance assessment phase accounted for significant variability. There were no indications for a substantial publication bias. Interpersonal problems of patients before psychotherapy are a robust predictor for lower therapeutic alliance quality, albeit a small effect size. Consequently, patients who experience interpersonal problems may face greater challenges in developing a strong alliance with their therapists, especially in early stages of the treatment. Clinical Impact Statement Question: How are patients' interpersonal problems at the beginning of a psychotherapy associated with the subsequent quality of the therapeutic alliance? Findings: Overall, there is a small but significant negative relationship between interpersonal problems at the beginning of psychotherapy and subsequent therapeutic alliance (r = −.12). Meaning: Individuals with higher levels of interpersonal problems may face greater challenges in developing a strong therapeutic alliance with their therapists. However, these interpersonal problems also appear to present an opportunity for fostering a strong alliance. Next Steps: Future research ought to focus on how therapists adequately manage patients' preexisting interpersonal problems.