Tumor sink effect (TSE) has been defined as; decreased uptake in healthy tissue with increased tumor sequestration of the radiopharmaceuticals. It enables us to give high tumoral radiation doses while resulting in lower absorbed radiation to critical organs. However, the factors which influence this effect are yet to be defined. In this study, we have investigated the predictive factors of the tumor sink effect in a group of patients who received 177Lu-Prostate-specific membrane antigen (PSMA) therapy due to progressive metastatic castration-resistant prostate cancer (mCRPC). We have retrospectively analyzed the pre-therapy 68Ga-PSMA positron-emission tomography (PET)-computed tomography (CT) and post-therapy planar whole-body scans of 65 patients who received at least two cycles of 7.4 GBq of 177Lu-PSMA therapy. All patients with mCRPC were referred to our department after multiple treatment lines. Age, previous therapies, International Society of Urological Pathology (ISUP) score, and pre-therapy serum tumor marker levels were recorded. Post 177Lu-PSMA therapy images were analyzed for TSE. 68Ga-PSMA PET-CT images were used for the calculation of SUVmax in malignant and healthy tissues as well as metabolic tumor volume (MTV) and total lesion PSMA index (TLPI). Based on the post-therapy scans, TSE was seen in 17/65 (26.2%) patients. In univariate analysis, patients with TSE had higher pre-therapy PSA, PSA velocity, and ALP (p