Abstract The use of interscalene blocks (ISBs) for shoulder surgery improves postoperative pain control, reduces recovery room times, and reduces overall hospital stays. The most common and potentially disabling adverse effect associated with ISBs is phrenic nerve paresis. Fortunately, persistent phrenic nerve paresis (PPNP) is rare. There are only 4 case reports of PPNP in the English literature. At our institution, we identified 9 cases of PPNP over a 9-year period, representing an incidence of 1 (0.048%) in 2069. In conducting a case-control series, we found that symptomatic cervical spine disease is a risk factor for the development of PPNP. Patients with PPNP had a significantly higher incidence of cervical spine disease (85.7%) compared with the control group (30.9%), P < 0.01. Persistent phrenic nerve paresis remains a perplexing complication of ISB, and many questions remain unanswered. Our data identify an important risk factor that can aid in the risk stratification of patients undergoing ISB.