Abstract Purpose The study aimed to evaluate the effect of androgen deprivation therapy (ADT) on PSMA imaging and its correlation to the PSA concentration by comparing qualitative and quantitative parameters: SUV_max, SUV_mean, PSMA-derived tumor volume (PSMA-TV), total lesion PSMA (TL-PSMA) and molecular imaging (mi)PSMA score. Methods Retrospective analysis of 21 therapy-naïve patients with oligometastatic prostate cancer (median age 70 years) who underwent either [⁶⁸Ga]Ga-PSMA-11-PET/CT or -PET/MRI before initiation of (T1) as well as during ADT (T2). The median duration of ADT was 155 days (range 61–289 days). All lesions were analyzed using several qualitative and quantitative PET parameters. Results A total of 109 PSMA-positive lesions (24 intraprostatic, 56 lymphonodal and 29 osseous) were visually detected at any of the examinations, while at T2, two new bone lesions were detected in one patient. During ADT, all patients experienced a decrease in their PSA level (median: 29.1 before vs. 0.71 after; p < 0.001). During long-term ADT, a relevant decrease in lesion count occurred, especially in patients with a T2 PSA value < 1 ng/ml (median: 4 vs. 0.9; p = 0.007) and PSMA expression, which resulted in miN- and/or miM-downstaging in 11 patients (52.7%). All analyzed PET parameters correlated strongly with each other. The PSA level at T2 correlated modestly with the decrease in PSMA expression and its derived volumes. Conclusion Post-ADT scans detected, especially in patients with a residual PSA < 1 ng/ml, fewer PSMA-positive lesions with overall lower PSMA expression, regardless of primary tumor site or metastatic sites. None of the PET parameters has proven to be superior, as they all correlated modestly with the PSA value at T2. Thus, the simply acquirable miPSMA score seems to be the most suitable for evaluating the effect of ADT on PSMA expression.