The ways in which prescription drug monitoring programs (PDMPs) have been integrated into clinical practice remain understudied, and research into PDMP implementation in states where PDMP use by providers is mandated remains scant. This qualitative study describes how use of a state-mandated PDMP influenced clinical practice and opioid analgesic prescribing. We conducted face-to-face, in-depth interviews with 53 New York State-licensed primary care physicians who reported that they currently prescribed opioid analgesic medication, including those providers who reported consistent use of the PDMP (n = 38) in this sample. We used a thematic analytic approach to identify patterns of PDMP implementation into practice following enactment of the New York State legislative usage mandate. Among physicians who consistently used the PDMP, we found two distinct groups: (1) physicians who reported no change in their clinical practice and (2) physicians who acknowledged changes to both clinical practice and administrative management. In the latter group, most physicians felt the PDMP had benefited their patient relationships by fostering dialogue around patient substance use; however, some used the PDMP to dismiss patients from care. Findings suggest that increased education for providers relating to judicious prescribing, opioid use disorder, and best practice for PDMP utilization are needed.